--- type: "firecrawl-provider" description: "gnomAD, the Genome Aggregation Database of the Broad Institute, through the public GraphQL API behind its browser: how often a variant occurs in 807,162 people (v4.1) by sequencing type (exomes, genomes, both combined) and genetic ancestry group, with homozygote and hemizygote counts, quality filters, the grpmax filtering allele frequency and its consequence on the MANE Select transcript with LOFTEE's loss-of-function call; a gene's constraint (pLI, LOEUF with its confidence interval and percentile, observed and expected pLoF, missense and synonymous variants, z scores); and the variants gnomAD lists in a gene, filtered by consequence, LOFTEE call and allele frequency. Takes gene symbols, Ensembl IDs, gnomAD variant IDs, rsIDs, ClinGen allele IDs and browser URLs, on gnomAD v4.1 and v3.1.2 (GRCh38) or v2.1.1 (GRCh37). Primary data is CC0: every answer carries gnomAD's attribution, citation and terms of use." use_when: "gnomAD, the Genome Aggregation Database of the Broad Institute, through the public GraphQL API behind its browser: how often a variant occurs in 807,162 people (v4.1) by sequencing type (exomes, genomes, both combined) and genetic ancestry group, with homozygote and hemizygote counts, quality filters, the grpmax filtering allele frequency and its consequence on the MANE Select transcript with LOFTEE's loss-of-function call; a gene's constraint (pLI, LOEUF with its confidence interval and percentile, observed and expected pLoF, missense and synonymous variants, z scores); and the variants gnomAD lists in a gene, filtered by consequence, LOFTEE call and allele frequency. Takes gene symbols, Ensembl IDs, gnomAD variant IDs, rsIDs, ClinGen allele IDs and browser URLs, on gnomAD v4.1 and v3.1.2 (GRCh38) or v2.1.1 (GRCh37). Primary data is CC0: every answer carries gnomAD's attribution, citation and terms of use.\n\ngnomAD, the Genome Aggregation Database of the Broad Institute, through the public GraphQL API behind its browser: how often a variant occurs in 807,162 people (v4.1) by sequencing type (exomes, genomes, both combined) and genetic ancestry group, with homozygote and hemizygote counts, quality filters, the grpmax filtering allele frequency and its consequence on the MANE Select transcript with LOFTEE's loss-of-function call; a gene's constraint (pLI, LOEUF with its confidence interval and percentile, observed and expected pLoF, missense and synonymous variants, z scores); and the variants gnomAD lists in a gene, filtered by consequence, LOFTEE call and allele frequency. Takes gene symbols, Ensembl IDs, gnomAD variant IDs, rsIDs, ClinGen allele IDs and browser URLs, on gnomAD v4.1 and v3.1.2 (GRCh38) or v2.1.1 (GRCh37). Primary data is CC0: every answer carries gnomAD's attribution, citation and terms of use." categories: "Life sciences" capabilities: 3 credits_per_call: 5 --- # Population allele frequencies and gene constraint (Broad Institute) on Firecrawl Alexandria gnomAD, the Genome Aggregation Database of the Broad Institute, through the public GraphQL API behind its browser: how often a variant occurs in 807,162 people (v4.1) by sequencing type (exomes, genomes, both combined) and genetic ancestry group, with homozygote and hemizygote counts, quality filters, the grpmax filtering allele frequency and its consequence on the MANE Select transcript with LOFTEE's loss-of-function call; a gene's constraint (pLI, LOEUF with its confidence interval and percentile, observed and expected pLoF, missense and synonymous variants, z scores); and the variants gnomAD lists in a gene, filtered by consequence, LOFTEE call and allele frequency. Takes gene symbols, Ensembl IDs, gnomAD variant IDs, rsIDs, ClinGen allele IDs and browser URLs, on gnomAD v4.1 and v3.1.2 (GRCh38) or v2.1.1 (GRCh37). Primary data is CC0: every answer carries gnomAD's attribution, citation and terms of use. - Categories: Life sciences - Category index: [Life sciences category](https://firecrawl.dev/alexandria/agents/categories/life-sciences) - Provider key: `gnomad-broadinstitute-org` - Access: Firecrawl credits - Cost: 5 credits per call ## More - [Human guide](https://firecrawl.dev/app/alexandria/gnomad-broadinstitute-org) - [OpenAPI spec](https://firecrawl.dev/alexandria/agents/providers/gnomad-broadinstitute-org/openapi.json) ## Capabilities - [Frequency](https://firecrawl.dev/alexandria/agents/providers/gnomad-broadinstitute-org/variants/frequency): One variant's allele frequencies in gnomAD, by gnomAD variant ID (19-44908684-T-C, also chr19:44908684:T:C or 19-44908684-T>C), rsID (rs429358), ClinGen allele ID (CA127512) or gnomAD variant page URL. For each sequencing type (exomes, genomes, and in v4 both combined) it returns allele count, allele number, frequency, homozygote and hemizygote counts, quality filters and flags, the grpmax filtering allele frequency (faf95) with its group, and a row per genetic ancestry group (African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Middle Eastern, European (non-Finnish), Amish, South Asian, Remaining), optionally split into XX and XY. Also the variant's rsIDs, CAID, co-located variants and, per gene, its consequence on the MANE Select (else canonical) transcript with HGVSc, HGVSp and LOFTEE's call. A multi-allelic rsID returns every allele. Variants gnomAD has not seen are not_found; a site where no alternate allele passed quality control is returned with AC 0 and its AC0 filter. - [Search](https://firecrawl.dev/alexandria/agents/providers/gnomad-broadinstitute-org/variants/search): The variants gnomAD lists in a gene, by HGNC symbol, Ensembl gene ID or gnomAD gene page URL, filtered and paged. Each row has the variant ID, rsIDs, the most severe consequence in the gene and its category (lof, missense, inframe, synonymous, splice_region, utr, intron, other), transcript, HGVSc, HGVSp, LOFTEE call and flags, variant flags, and AC, AN, AF, homozygote count and quality filters for exomes, genomes and (v4) both combined. Filter by consequence categories, LOFTEE high-confidence pLoF only, and a minimum and maximum allele frequency (joint in v4, else exomes and genomes summed); sort by position or by frequency, highest first. The whole gene is read in one request (TTN, the largest, has 112,412 variants). total_in_gene and total count the gene's variants and the matches; unknown genes are not_found. - [Constraint](https://firecrawl.dev/alexandria/agents/providers/gnomad-broadinstitute-org/genes/constraint): gnomAD's constraint metrics for one gene, by HGNC symbol (PCSK9), Ensembl gene ID with or without version (ENSG00000169174.11) or gnomAD gene page URL, on GRCh38 (gnomAD v4.1.2 constraint, the default) or GRCh37 (v2.1.1). Returns the gene's identity (Ensembl ID and version, symbol, name, HGNC, NCBI Gene and OMIM IDs, location, Ensembl canonical and MANE Select transcripts) and its constraint: pLI, LOEUF with its LOEUF percentile, and for pLoF, missense and synonymous variants the observed and expected counts, observed/expected ratio with its 90% confidence interval and z score, plus gnomAD's gene and constraint flags. Genes gnomAD computes no constraint for (most non-coding genes) return constraint null with a no_constraint warning; unknown genes are not_found. ## 1. Choose this provider when gnomAD, the Genome Aggregation Database of the Broad Institute, through the public GraphQL API behind its browser: how often a variant occurs in 807,162 people (v4.1) by sequencing type (exomes, genomes, both combined) and genetic ancestry group, with homozygote and hemizygote counts, quality filters, the grpmax filtering allele frequency and its consequence on the MANE Select transcript with LOFTEE's loss-of-function call; a gene's constraint (pLI, LOEUF with its confidence interval and percentile, observed and expected pLoF, missense and synonymous variants, z scores); and the variants gnomAD lists in a gene, filtered by consequence, LOFTEE call and allele frequency. Takes gene symbols, Ensembl IDs, gnomAD variant IDs, rsIDs, ClinGen allele IDs and browser URLs, on gnomAD v4.1 and v3.1.2 (GRCh38) or v2.1.1 (GRCh37). Primary data is CC0: every answer carries gnomAD's attribution, citation and terms of use. gnomAD, the Genome Aggregation Database of the Broad Institute, through the public GraphQL API behind its browser: how often a variant occurs in 807,162 people (v4.1) by sequencing type (exomes, genomes, both combined) and genetic ancestry group, with homozygote and hemizygote counts, quality filters, the grpmax filtering allele frequency and its consequence on the MANE Select transcript with LOFTEE's loss-of-function call; a gene's constraint (pLI, LOEUF with its confidence interval and percentile, observed and expected pLoF, missense and synonymous variants, z scores); and the variants gnomAD lists in a gene, filtered by consequence, LOFTEE call and allele frequency. Takes gene symbols, Ensembl IDs, gnomAD variant IDs, rsIDs, ClinGen allele IDs and browser URLs, on gnomAD v4.1 and v3.1.2 (GRCh38) or v2.1.1 (GRCh37). Primary data is CC0: every answer carries gnomAD's attribution, citation and terms of use. ## 2. Minimal request Call `POST https://api.firecrawl.dev/v2/scrape` with `{ alexandria: { provider, capability, options } }`. For a batch, send `{ alexandria: [...] }` with up to 10 calls. ```json { "provider": "gnomad-broadinstitute-org", "capability": "variants/frequency", "options": { "variant": "rs429358" } } ``` ## 3. Add provider options Use only the options needed for the task: - `by_sex` (boolean): Add XX and XY counts for every genetic ancestry group and overall. Example: `false` - `dataset` (string): gnomad_r4 (v4.1, 730,947 exomes and 76,215 genomes, GRCh38; the default), gnomad_r3 (v3.1.2, 76,156 genomes, GRCh38) or gnomad_r2_1 (v2.1.1, 125,748 exomes and 15,708 genomes, GRCh37). Defaults to the dataset of a pasted browser URL, else gnomad_r4. Example: `gnomad_r4` - `variant` (string, required): gnomAD variant ID ("19-44908684-T-C", "chr19:44908684:T:C"), rsID ("rs429358"), ClinGen allele ID ("CA127512") or gnomAD variant page URL. Coordinates are on the dataset's reference genome. Example: `` ## 4. Request through your preferred interface ### JavaScript ```javascript const result = await firecrawl.scrape({ alexandria: { provider: "gnomad-broadinstitute-org", capability: "variants/frequency", options: { variant: "rs429358", }, }, }); ``` ### Python ```python result = firecrawl.scrape_alexandria({ "provider": "gnomad-broadinstitute-org", "capability": "variants/frequency", "options": { "variant": "rs429358" } }) ``` ### cURL ```sh curl https://api.firecrawl.dev/v2/scrape \ -H "Authorization: Bearer $FIRECRAWL_API_KEY" \ -H "Content-Type: application/json" \ -d '{ "alexandria": { "provider": "gnomad-broadinstitute-org", "capability": "variants/frequency", "options": { "variant": "rs429358" } } }' ``` ### CLI ```sh firecrawl scrape 'gnomad-broadinstitute-org/variants/frequency' \ --options '{"variant":"rs429358"}' ``` ### MCP Call the FCX MCP retrieve tool with this object: ```json { "provider": "gnomad-broadinstitute-org", "capability": "variants/frequency", "options": { "variant": "rs429358" } } ``` Ask for only the returned fields needed by the task. ## 5. Full request shape ```json { "provider": "gnomad-broadinstitute-org", "capability": "variants/frequency", "options": { "variant": "rs429358" } } ``` ## 6. Response data The response includes `success`, `provider`, `capability`, `creditsCost` and `data`. This example shows the provider payload in `data`: ```json { "dataset": "gnomad_r4", "dataset_version": "gnomAD v4.1.2", "license": { "attribution": "This tool includes data from the gnomAD v4.1.2 release (Genome Aggregation Database, Broad Institute), https://gnomad.broadinstitute.org/. Source: https://gnomad.broadinstitute.org/variant/19-44908684-T-C?dataset=gnomad_r4. gnomAD asks that uses of its data cite its flagship paper and link to the browser.", "citation": "Guez J, Goodrich JK, Moldovan MA, et al. Integrating 730,947 exome sequences with clinical literature improves gene discovery. medRxiv [Preprint] (2026). https://doi.org/10.64898/2026.03.23.26349081", "name": "CC0 1.0 (gnomAD primary data)", "terms": "All users of gnomAD data agree to not attempt to reidentify participants. (gnomAD terms of use, https://gnomad.broadinstitute.org/policies)", "url": "https://creativecommons.org/publicdomain/zero/1.0/" }, "observed_at_ms": 1793397648465, "query": "rs429358", "query_type": "rsid", "reference_genome": "GRCh38", "variants": [ { "alt": "C", "caid": "CA127512", "chrom": "19", "colocated_variants": [ "19-44908684-TGCGGCC-T" ], "exome": { "ac": 208931, "af": 0.14757098460234497, "an": 1415800, "by_sex": null, "faf95": { "faf": 0.2222636, "group": "afr", "group_label": "African/African American" }, "filters": [], "flags": [], "hemizygote_count": 0, "homozygote_count": 15700, "populations": [ { "ac": 7291, "af": 0.22661154969851433, "an": 32174, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 817, "id": "afr", "label": "African/African American" }, { "ac": 3877, "af": 0.10427088376095961, "an": 37182, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 204, "id": "amr", "label": "Admixed American" }, { "ac": 3045, "af": 0.12045094936708861, "an": 25280, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 177, "id": "asj", "label": "Ashkenazi Jewish" }, { "ac": 3591, "af": 0.09785274401874762, "an": 36698, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 166, "id": "eas", "label": "East Asian" }, { "ac": 9464, "af": 0.19123055162659122, "an": 49490, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 911, "id": "fin", "label": "European (Finnish)" }, { "ac": 384, "af": 0.06806097128677774, "an": 5642, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 15, "id": "mid", "label": "Middle Eastern" }, { "ac": 164927, "af": 0.15142197673863464, "an": 1089188, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 12315, "id": "nfe", "label": "European (non-Finnish)" }, { "ac": 8181, "af": 0.10039761431411531, "an": 81486, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 486, "id": "sas", "label": "South Asian" }, { "ac": 8171, "af": 0.13929423798158883, "an": 58660, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 609, "id": "remaining", "label": "Remaining" } ] }, "flags": [], "gene_consequences": [ { "consequence": "missense_variant", "consequence_terms": [ "missense_variant" ], "ensembl_gene_id": "ENSG00000130203", "gene_symbol": "APOE", "hgvsc": "c.388T>C", "hgvsp": "p.Cys130Arg", "is_canonical": true, "is_mane_select": true, "loftee": null, "refseq_id": "NM_000041", "refseq_version": "4", "transcript_id": "ENST00000252486", "transcript_version": "9" } ], "genome": { "ac": 23933, "af": 0.1573587039423507, "an": 152092, "by_sex": null, "faf95": { "faf": 0.21196047, "group": "afr", "group_label": "African/African American" }, "filters": [], "flags": [], "hemizygote_count": 0, "homozygote_count": 2010, "populations": [ { "ac": 8954, "af": 0.21569666602428214, "an": 41512, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 955, "id": "afr", "label": "African/African American" }, { "ac": 1734, "af": 0.11333333333333333, "an": 15300, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 95, "id": "amr", "label": "Admixed American" }, { "ac": 413, "af": 0.11908881199538639, "an": 3468, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 20, "id": "asj", "label": "Ashkenazi Jewish" }, { "ac": 503, "af": 0.09770784770784771, "an": 5148, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 17, "id": "eas", "label": "East Asian" }, { "ac": 2069, "af": 0.19518867924528302, "an": 10600, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 189, "id": "fin", "label": "European (Finnish)" }, { "ac": 20, "af": 0.0684931506849315, "an": 292, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 1, "id": "mid", "label": "Middle Eastern" }, { "ac": 9368, "af": 0.13793509629542375, "an": 67916, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 676, "id": "nfe", "label": "European (non-Finnish)" }, { "ac": 124, "af": 0.13626373626373625, "an": 910, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 7, "id": "ami", "label": "Amish" }, { "ac": 505, "af": 0.10455486542443064, "an": 4830, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 36, "id": "sas", "label": "South Asian" }, { "ac": 243, "af": 0.11483931947069943, "an": 2116, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 14, "id": "remaining", "label": "Remaining" } ] }, "gnomad_url": "https://gnomad.broadinstitute.org/variant/19-44908684-T-C?dataset=gnomad_r4", "joint": { "ac": 232864, "af": 0.14852043380538965, "an": 1567892, "by_sex": null, "faf95": { "faf": 0.21762494, "group": "afr", "group_label": "African/African American" }, "filters": [ "discrepant_frequencies" ], "flags": [], "hemizygote_count": 0, "homozygote_count": 17710, "populations": [ { "ac": 16245, "af": 0.22046250305349727, "an": 73686, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 1772, "id": "afr", "label": "African/African American" }, { "ac": 5611, "af": 0.10691284630921077, "an": 52482, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 299, "id": "amr", "label": "Admixed American" }, { "ac": 3458, "af": 0.12028662863503548, "an": 28748, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 197, "id": "asj", "label": "Ashkenazi Jewish" }, { "ac": 4094, "af": 0.09783491851072981, "an": 41846, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 183, "id": "eas", "label": "East Asian" }, { "ac": 11533, "af": 0.19192877350640705, "an": 60090, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 1100, "id": "fin", "label": "European (Finnish)" }, { "ac": 404, "af": 0.06808223795079205, "an": 5934, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 16, "id": "mid", "label": "Middle Eastern" }, { "ac": 174295, "af": 0.15063036684688672, "an": 1157104, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 12991, "id": "nfe", "label": "European (non-Finnish)" }, { "ac": 124, "af": 0.13626373626373625, "an": 910, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 7, "id": "ami", "label": "Amish" }, { "ac": 8686, "af": 0.10063024236526252, "an": 86316, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 522, "id": "sas", "label": "South Asian" }, { "ac": 8414, "af": 0.1384428063709359, "an": 60776, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 623, "id": "remaining", "label": "Remaining" } ] }, "pos": 44908684, "ref": "T", "rsids": [ "rs429358" ], "variant_id": "19-44908684-T-C" } ] } ``` ## API reference-derived contract The following capability contract is generated from the same normalized Alexandria API reference exposed in the API spec. ### Frequency - Capability: `variants/frequency` - Description: One variant's allele frequencies in gnomAD, by gnomAD variant ID (19-44908684-T-C, also chr19:44908684:T:C or 19-44908684-T>C), rsID (rs429358), ClinGen allele ID (CA127512) or gnomAD variant page URL. For each sequencing type (exomes, genomes, and in v4 both combined) it returns allele count, allele number, frequency, homozygote and hemizygote counts, quality filters and flags, the grpmax filtering allele frequency (faf95) with its group, and a row per genetic ancestry group (African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Middle Eastern, European (non-Finnish), Amish, South Asian, Remaining), optionally split into XX and XY. Also the variant's rsIDs, CAID, co-located variants and, per gene, its consequence on the MANE Select (else canonical) transcript with HGVSc, HGVSp and LOFTEE's call. A multi-allelic rsID returns every allele. Variants gnomAD has not seen are not_found; a site where no alternate allele passed quality control is returned with AC 0 and its AC0 filter. - Instructions: To see how common a variant is in the general population and in which genetic ancestry groups, e.g. to rule out a candidate as too common for a rare disease (compare faf95 with the maximum credible frequency) or to read carrier and homozygote counts. Use search to list a gene's variants and constraint for gene-level tolerance. For clinical significance use the ClinVar program; for predicted pathogenicity of missense changes alphafold-ebi-ac-uk variants/missense; for consequences on every transcript the Ensembl program. - Cost: 5 credits per call - Capability file: [Frequency](https://firecrawl.dev/alexandria/agents/providers/gnomad-broadinstitute-org/variants/frequency) Accepted options: - `by_sex` (boolean): Add XX and XY counts for every genetic ancestry group and overall. Example: `false` - `dataset` (string): gnomad_r4 (v4.1, 730,947 exomes and 76,215 genomes, GRCh38; the default), gnomad_r3 (v3.1.2, 76,156 genomes, GRCh38) or gnomad_r2_1 (v2.1.1, 125,748 exomes and 15,708 genomes, GRCh37). Defaults to the dataset of a pasted browser URL, else gnomad_r4. Example: `gnomad_r4` - `variant` (string, required): gnomAD variant ID ("19-44908684-T-C", "chr19:44908684:T:C"), rsID ("rs429358"), ClinGen allele ID ("CA127512") or gnomAD variant page URL. Coordinates are on the dataset's reference genome. Example: `` Response schema example: ```json { "dataset": "gnomad_r4", "dataset_version": "gnomAD v4.1.2", "license": { "attribution": "This tool includes data from the gnomAD v4.1.2 release (Genome Aggregation Database, Broad Institute), https://gnomad.broadinstitute.org/. Source: https://gnomad.broadinstitute.org/variant/19-44908684-T-C?dataset=gnomad_r4. gnomAD asks that uses of its data cite its flagship paper and link to the browser.", "citation": "Guez J, Goodrich JK, Moldovan MA, et al. Integrating 730,947 exome sequences with clinical literature improves gene discovery. medRxiv [Preprint] (2026). https://doi.org/10.64898/2026.03.23.26349081", "name": "CC0 1.0 (gnomAD primary data)", "terms": "All users of gnomAD data agree to not attempt to reidentify participants. (gnomAD terms of use, https://gnomad.broadinstitute.org/policies)", "url": "https://creativecommons.org/publicdomain/zero/1.0/" }, "observed_at_ms": 1793397648465, "query": "rs429358", "query_type": "rsid", "reference_genome": "GRCh38", "variants": [ { "alt": "C", "caid": "CA127512", "chrom": "19", "colocated_variants": [ "19-44908684-TGCGGCC-T" ], "exome": { "ac": 208931, "af": 0.14757098460234497, "an": 1415800, "by_sex": null, "faf95": { "faf": 0.2222636, "group": "afr", "group_label": "African/African American" }, "filters": [], "flags": [], "hemizygote_count": 0, "homozygote_count": 15700, "populations": [ { "ac": 7291, "af": 0.22661154969851433, "an": 32174, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 817, "id": "afr", "label": "African/African American" }, { "ac": 3877, "af": 0.10427088376095961, "an": 37182, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 204, "id": "amr", "label": "Admixed American" }, { "ac": 3045, "af": 0.12045094936708861, "an": 25280, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 177, "id": "asj", "label": "Ashkenazi Jewish" }, { "ac": 3591, "af": 0.09785274401874762, "an": 36698, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 166, "id": "eas", "label": "East Asian" }, { "ac": 9464, "af": 0.19123055162659122, "an": 49490, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 911, "id": "fin", "label": "European (Finnish)" }, { "ac": 384, "af": 0.06806097128677774, "an": 5642, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 15, "id": "mid", "label": "Middle Eastern" }, { "ac": 164927, "af": 0.15142197673863464, "an": 1089188, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 12315, "id": "nfe", "label": "European (non-Finnish)" }, { "ac": 8181, "af": 0.10039761431411531, "an": 81486, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 486, "id": "sas", "label": "South Asian" }, { "ac": 8171, "af": 0.13929423798158883, "an": 58660, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 609, "id": "remaining", "label": "Remaining" } ] }, "flags": [], "gene_consequences": [ { "consequence": "missense_variant", "consequence_terms": [ "missense_variant" ], "ensembl_gene_id": "ENSG00000130203", "gene_symbol": "APOE", "hgvsc": "c.388T>C", "hgvsp": "p.Cys130Arg", "is_canonical": true, "is_mane_select": true, "loftee": null, "refseq_id": "NM_000041", "refseq_version": "4", "transcript_id": "ENST00000252486", "transcript_version": "9" } ], "genome": { "ac": 23933, "af": 0.1573587039423507, "an": 152092, "by_sex": null, "faf95": { "faf": 0.21196047, "group": "afr", "group_label": "African/African American" }, "filters": [], "flags": [], "hemizygote_count": 0, "homozygote_count": 2010, "populations": [ { "ac": 8954, "af": 0.21569666602428214, "an": 41512, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 955, "id": "afr", "label": "African/African American" }, { "ac": 1734, "af": 0.11333333333333333, "an": 15300, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 95, "id": "amr", "label": "Admixed American" }, { "ac": 413, "af": 0.11908881199538639, "an": 3468, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 20, "id": "asj", "label": "Ashkenazi Jewish" }, { "ac": 503, "af": 0.09770784770784771, "an": 5148, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 17, "id": "eas", "label": "East Asian" }, { "ac": 2069, "af": 0.19518867924528302, "an": 10600, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 189, "id": "fin", "label": "European (Finnish)" }, { "ac": 20, "af": 0.0684931506849315, "an": 292, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 1, "id": "mid", "label": "Middle Eastern" }, { "ac": 9368, "af": 0.13793509629542375, "an": 67916, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 676, "id": "nfe", "label": "European (non-Finnish)" }, { "ac": 124, "af": 0.13626373626373625, "an": 910, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 7, "id": "ami", "label": "Amish" }, { "ac": 505, "af": 0.10455486542443064, "an": 4830, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 36, "id": "sas", "label": "South Asian" }, { "ac": 243, "af": 0.11483931947069943, "an": 2116, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 14, "id": "remaining", "label": "Remaining" } ] }, "gnomad_url": "https://gnomad.broadinstitute.org/variant/19-44908684-T-C?dataset=gnomad_r4", "joint": { "ac": 232864, "af": 0.14852043380538965, "an": 1567892, "by_sex": null, "faf95": { "faf": 0.21762494, "group": "afr", "group_label": "African/African American" }, "filters": [ "discrepant_frequencies" ], "flags": [], "hemizygote_count": 0, "homozygote_count": 17710, "populations": [ { "ac": 16245, "af": 0.22046250305349727, "an": 73686, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 1772, "id": "afr", "label": "African/African American" }, { "ac": 5611, "af": 0.10691284630921077, "an": 52482, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 299, "id": "amr", "label": "Admixed American" }, { "ac": 3458, "af": 0.12028662863503548, "an": 28748, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 197, "id": "asj", "label": "Ashkenazi Jewish" }, { "ac": 4094, "af": 0.09783491851072981, "an": 41846, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 183, "id": "eas", "label": "East Asian" }, { "ac": 11533, "af": 0.19192877350640705, "an": 60090, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 1100, "id": "fin", "label": "European (Finnish)" }, { "ac": 404, "af": 0.06808223795079205, "an": 5934, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 16, "id": "mid", "label": "Middle Eastern" }, { "ac": 174295, "af": 0.15063036684688672, "an": 1157104, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 12991, "id": "nfe", "label": "European (non-Finnish)" }, { "ac": 124, "af": 0.13626373626373625, "an": 910, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 7, "id": "ami", "label": "Amish" }, { "ac": 8686, "af": 0.10063024236526252, "an": 86316, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 522, "id": "sas", "label": "South Asian" }, { "ac": 8414, "af": 0.1384428063709359, "an": 60776, "by_sex": null, "hemizygote_count": 0, "homozygote_count": 623, "id": "remaining", "label": "Remaining" } ] }, "pos": 44908684, "ref": "T", "rsids": [ "rs429358" ], "variant_id": "19-44908684-T-C" } ] } ``` ### Search - Capability: `variants/search` - Description: The variants gnomAD lists in a gene, by HGNC symbol, Ensembl gene ID or gnomAD gene page URL, filtered and paged. Each row has the variant ID, rsIDs, the most severe consequence in the gene and its category (lof, missense, inframe, synonymous, splice_region, utr, intron, other), transcript, HGVSc, HGVSp, LOFTEE call and flags, variant flags, and AC, AN, AF, homozygote count and quality filters for exomes, genomes and (v4) both combined. Filter by consequence categories, LOFTEE high-confidence pLoF only, and a minimum and maximum allele frequency (joint in v4, else exomes and genomes summed); sort by position or by frequency, highest first. The whole gene is read in one request (TTN, the largest, has 112,412 variants). total_in_gene and total count the gene's variants and the matches; unknown genes are not_found. - Instructions: To survey a gene's population variation: its loss-of-function or missense variants, the common ones, or those within a frequency band, e.g. to find known pLoF carriers in a candidate gene. Use frequency for one variant's full ancestry breakdown and constraint for gene-level tolerance; for clinically classified variants use the ClinVar program. - Cost: 5 credits per call - Capability file: [Search](https://firecrawl.dev/alexandria/agents/providers/gnomad-broadinstitute-org/variants/search) Accepted options: - `consequences` (string[]): Keep these consequence categories: lof (stop gained, frameshift, splice donor or acceptor, transcript ablation), missense (also start and stop lost), inframe, synonymous, splice_region, utr, intron, other. All when absent. Example: `[]` - `dataset` (string): gnomad_r4 (v4.1, 730,947 exomes and 76,215 genomes, GRCh38; the default), gnomad_r3 (v3.1.2, 76,156 genomes, GRCh38) or gnomad_r2_1 (v2.1.1, 125,748 exomes and 15,708 genomes, GRCh37). Defaults to the dataset of a pasted browser URL, else gnomad_r4. Example: `gnomad_r4` - `gene` (string, required): HGNC symbol ("PCSK9"), Ensembl gene ID ("ENSG00000169174", version optional) or gnomAD gene page URL. Example: `` - `limit` (number): Variants per page. Example: `25` - `loftee_hc_only` (boolean): Keep only LOFTEE high-confidence pLoF variants. Example: `false` - `max_af` (number): Keep variants with at most this allele frequency. Example: `1` - `min_af` (number): Keep variants with at least this allele frequency. Example: `1` - `offset` (number): Matching variants to skip. Example: `0` - `sort` (string): position (genomic order) or af_desc (most common first). Example: `position` Response schema example: ```json { "dataset": "gnomad_r4", "dataset_version": "gnomAD v4.1.2", "filters": { "consequences": [ "lof" ], "loftee_hc_only": true, "max_af": null, "min_af": null, "sort": "position" }, "gene": { "canonical_transcript_id": "ENST00000302118", "chrom": "1", "ensembl_gene_id": "ENSG00000169174", "mane_select": { "ensembl_id": "ENST00000302118", "ensembl_version": "5", "refseq_id": "NM_174936", "refseq_version": "4" }, "start": 55039447, "stop": 55064852, "symbol": "PCSK9" }, "gnomad_url": "https://gnomad.broadinstitute.org/gene/ENSG00000169174?dataset=gnomad_r4", "license": { "attribution": "This tool includes data from the gnomAD v4.1.2 release (Genome Aggregation Database, Broad Institute), https://gnomad.broadinstitute.org/. Source: https://gnomad.broadinstitute.org/gene/ENSG00000169174?dataset=gnomad_r4. gnomAD asks that uses of its data cite its flagship paper and link to the browser.", "citation": "Guez J, Goodrich JK, Moldovan MA, et al. Integrating 730,947 exome sequences with clinical literature improves gene discovery. medRxiv [Preprint] (2026). https://doi.org/10.64898/2026.03.23.26349081", "name": "CC0 1.0 (gnomAD primary data)", "terms": "All users of gnomAD data agree to not attempt to reidentify participants. (gnomAD terms of use, https://gnomad.broadinstitute.org/policies)", "url": "https://creativecommons.org/publicdomain/zero/1.0/" }, "next_offset": 10, "observed_at_ms": 1793397698047, "offset": 0, "query": "PCSK9", "reference_genome": "GRCh38", "total": 181, "total_in_gene": 4544, "variants": [ { "af": 0, "consequence": "stop_gained", "consequence_category": "lof", "exome": { "ac": 0, "af": 0, "an": 1410978, "filters": [ "AC0" ], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.29G>A", "hgvsp": "p.Trp10Ter", "joint": { "ac": 0, "af": 0, "an": 1562614, "filters": [ "AC0" ], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039866, "rsids": [], "transcript_id": "ENST00000302118", "variant_id": "1-55039866-G-A" }, { "af": 6.401491291411247e-7, "consequence": "stop_gained", "consequence_category": "lof", "exome": { "ac": 1, "af": 7.087342997634244e-7, "an": 1410966, "filters": [], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.33G>A", "hgvsp": "p.Trp11Ter", "joint": { "ac": 1, "af": 6.401491291411247e-7, "an": 1562136, "filters": [], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039870, "rsids": [ "rs1164872643" ], "transcript_id": "ENST00000302118", "variant_id": "1-55039870-G-A" }, { "af": 0.000003191739268095885, "consequence": "frameshift_variant", "consequence_category": "lof", "exome": { "ac": 5, "af": 0.0000035355078120580614, "an": 1414224, "filters": [], "homozygote_count": 0 }, "flags": [ "lof_flag", "lcr" ], "genome": null, "hgvsc": "c.65_66insG", "hgvsp": "p.Leu23ProfsTer148", "joint": { "ac": 5, "af": 0.000003191739268095885, "an": 1566544, "filters": [], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039902, "rsids": [], "transcript_id": "ENST00000302118", "variant_id": "1-55039902-T-TG" }, { "af": 0.000002572827086723569, "consequence": "frameshift_variant", "consequence_category": "lof", "exome": { "ac": 4, "af": 0.0000028468535151523777, "an": 1405060, "filters": [], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.66_67insT", "hgvsp": "p.Leu23SerfsTer148", "joint": { "ac": 4, "af": 0.000002572827086723569, "an": 1554710, "filters": [], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039903, "rsids": [], "transcript_id": "ENST00000302118", "variant_id": "1-55039903-C-CT" }, { "af": 6.432067716808922e-7, "consequence": "frameshift_variant", "consequence_category": "lof", "exome": { "ac": 1, "af": 7.117133787880944e-7, "an": 1405060, "filters": [], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.66_67insTT", "hgvsp": "p.Leu23PhefsTer22", "joint": { "ac": 1, "af": 6.432067716808922e-7, "an": 1554710, "filters": [], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039903, "rsids": [], "transcript_id": "ENST00000302118", "variant_id": "1-55039903-C-CTT" }, { "af": 0.0000031940922070538334, "consequence": "frameshift_variant", "consequence_category": "lof", "exome": { "ac": 5, "af": 0.000003538029572266377, "an": 1413216, "filters": [], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.75del", "hgvsp": "p.Ala26ArgfsTer18", "joint": { "ac": 5, "af": 0.0000031940922070538334, "an": 1565390, "filters": [], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039909, "rsids": [ "rs775052433" ], "transcript_id": "ENST00000302118", "variant_id": "1-55039909-TC-T" }, { "af": 6.381751254652296e-7, "consequence": "frameshift_variant", "consequence_category": "lof", "exome": { "ac": 1, "af": 7.069206114014984e-7, "an": 1414586, "filters": [ "AS_VQSR" ], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.79_80del", "hgvsp": "p.Gly27ArgfsTer143", "joint": { "ac": 1, "af": 6.381751254652296e-7, "an": 1566968, "filters": [], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039914, "rsids": [], "transcript_id": "ENST00000302118", "variant_id": "1-55039914-CGG-C" }, { "af": 0, "consequence": "frameshift_variant", "consequence_category": "lof", "exome": { "ac": 0, "af": 0, "an": 1415904, "filters": [ "AC0" ], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.85del", "hgvsp": "p.Arg29ValfsTer15", "joint": { "ac": 0, "af": 0, "an": 1568294, "filters": [ "AC0" ], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039919, "rsids": [ "rs1553135406" ], "transcript_id": "ENST00000302118", "variant_id": "1-55039919-GC-G" }, { "af": 0.00003757176844582788, "consequence": "frameshift_variant", "consequence_category": "lof", "exome": { "ac": 58, "af": 0.000040901583737530305, "an": 1418038, "filters": [], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": { "ac": 1, "af": 0.000006566419331538512, "an": 152290, "filters": [], "homozygote_count": 0 }, "hgvsc": "c.89_92dup", "hgvsp": "p.Gln31HisfsTer141", "joint": { "ac": 59, "af": 0.00003757176844582788, "an": 1570328, "filters": [], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039925, "rsids": [ "rs1344705474" ], "transcript_id": "ENST00000302118", "variant_id": "1-55039925-G-GCGCA" }, { "af": 0, "consequence": "stop_gained", "consequence_category": "lof", "exome": { "ac": 0, "af": 0, "an": 1418842, "filters": [ "AC0" ], "homozygote_count": 0 }, "flags": [ "lof_flag" ], "genome": null, "hgvsc": "c.91C>T", "hgvsp": "p.Gln31Ter", "joint": { "ac": 0, "af": 0, "an": 1571236, "filters": [ "AC0" ], "homozygote_count": 0 }, "loftee": { "call": "HC", "filters": [], "flags": [ "PHYLOCSF_WEAK" ] }, "pos": 55039928, "rsids": [], "transcript_id": "ENST00000302118", "variant_id": "1-55039928-C-T" } ] } ``` ### Constraint - Capability: `genes/constraint` - Description: gnomAD's constraint metrics for one gene, by HGNC symbol (PCSK9), Ensembl gene ID with or without version (ENSG00000169174.11) or gnomAD gene page URL, on GRCh38 (gnomAD v4.1.2 constraint, the default) or GRCh37 (v2.1.1). Returns the gene's identity (Ensembl ID and version, symbol, name, HGNC, NCBI Gene and OMIM IDs, location, Ensembl canonical and MANE Select transcripts) and its constraint: pLI, LOEUF with its LOEUF percentile, and for pLoF, missense and synonymous variants the observed and expected counts, observed/expected ratio with its 90% confidence interval and z score, plus gnomAD's gene and constraint flags. Genes gnomAD computes no constraint for (most non-coding genes) return constraint null with a no_constraint warning; unknown genes are not_found. - Instructions: To judge how tolerant a gene is to loss-of-function or missense variation, e.g. whether a heterozygous pLoF is plausibly pathogenic, or to rank candidate genes. Use frequency for one variant and search for a gene's variants. platform-opentargets-org get_target also shows LOEUF but not the counts, confidence interval or missense constraint; resolve aliases and previous symbols with genenames-org first, since gnomAD knows current symbols only. - Cost: 5 credits per call - Capability file: [Constraint](https://firecrawl.dev/alexandria/agents/providers/gnomad-broadinstitute-org/genes/constraint) Accepted options: - `gene` (string, required): HGNC symbol ("PCSK9"), Ensembl gene ID ("ENSG00000169174", version optional) or gnomAD gene page URL. Example: `` - `reference_genome` (string): GRCh38 for gnomAD v4.1.2 constraint (the default) or GRCh37 for v2.1.1. A pasted URL's dataset picks it when this is absent. Example: `GRCh38` Response schema example: ```json { "constraint": { "flags": [], "loeuf": 1.1441346736692857, "lof": { "expected": 62.116009290752274, "loeuf_percentile": 71, "observed": 57, "oe": 0.9176378304213768, "oe_lower": 0.7416265467075939, "oe_upper": 1.1441346736692857, "pli": 2.7651871109177563e-18, "z": 0.5506733800624033 }, "missense": { "expected": 959.787192434242, "observed": 870, "oe": 0.906450937101462, "oe_lower": 0.857514089563757, "oe_upper": 0.9586561741086428, "z": 1.2360458676592712 }, "pli": 2.7651871109177563e-18, "synonymous": { "expected": 409.3918482855569, "observed": 387, "oe": 0.9453046063830312, "oe_lower": 0.8700186318667248, "oe_upper": 1.028252849618702, "z": 0.6603188478981492 }, "transcript_id": "ENST00000302118", "version": "gnomAD v4.1.2" }, "gene": { "canonical_transcript_id": "ENST00000302118", "chrom": "1", "ensembl_gene_id": "ENSG00000169174", "ensembl_gene_version": "11", "flags": [], "hgnc_id": "HGNC:20001", "mane_select": { "ensembl_id": "ENST00000302118", "ensembl_version": "5", "refseq_id": "NM_174936", "refseq_version": "4" }, "name": "proprotein convertase subtilisin/kexin type 9", "ncbi_gene_id": "255738", "omim_id": "607786", "start": 55039447, "stop": 55064852, "strand": "+", "symbol": "PCSK9" }, "gnomad_url": "https://gnomad.broadinstitute.org/gene/ENSG00000169174?dataset=gnomad_r4", "license": { "attribution": "This tool includes data from the gnomAD v4.1.2 release (Genome Aggregation Database, Broad Institute), https://gnomad.broadinstitute.org/. Source: https://gnomad.broadinstitute.org/gene/ENSG00000169174?dataset=gnomad_r4. gnomAD asks that uses of its data cite its flagship paper and link to the browser.", "citation": "Guez J, Goodrich JK, Moldovan MA, et al. Integrating 730,947 exome sequences with clinical literature improves gene discovery. medRxiv [Preprint] (2026). https://doi.org/10.64898/2026.03.23.26349081", "name": "CC0 1.0 (gnomAD primary data)", "terms": "All users of gnomAD data agree to not attempt to reidentify participants. (gnomAD terms of use, https://gnomad.broadinstitute.org/policies)", "url": "https://creativecommons.org/publicdomain/zero/1.0/" }, "observed_at_ms": 1793397611895, "query": "PCSK9", "reference_genome": "GRCh38" } ```