Different results for clinvar Germline classification through API and the Gnomad download via website

General
1

For eg:- If I take the Gene BRCA1, I notice that some variants like “17-43124023-G-A” gives Clinical Germline Classification as “Conflicting classifications of pathogenicity”. But when I retrieve using API, I am getting it as “Likely pathogenic”. When I checked in NCBI Clinvar there also it shows “Likely pathogenic” as the Clinical Germline Classification. Why am I getting this difference while retrieving from website and API? And should I take the API one as correct as it is matching with the Clinvar website itself.

Below is the Graphql Code which I am using to get the Clinvar Germline Classsification using the API which is represented in the clinical_significance.

{
gene(gene_symbol: “BRCA1”, reference_genome: GRCh38) {
variants(dataset: gnomad_r4) {
variant_id
joint{
ac
an
fafmax {
faf95_max
}
}
}
clinvar_variants {
variant_id
clinical_significance
}

  }

}
2

Hi @Diya,

Thanks for writing in. This particular variant appears to have had the germline classification changed in ClinVar recently. The browser currently shows the data from ClinVar’s Apr 29, 2025 release, as some amount of data is still in our cached at various layers that help to make our frontend more performant.

Direct calls to the API do not hit these caching layers, so calls to the API are more accurate in this case. This happens for a brief period of time when we update our copy of the ClinVar data, which in this case we did late last week.

If you add the meta parameter to your GraphQL request, and get the clinvar_release_date:

{
  meta {
    clinvar_release_date
  }
  gene(gene_symbol: "BRCA1", reference_genome: GRCh38) {
    variants(dataset: gnomad_r4) {
      variant_id
      joint {
        ac
        an
        fafmax {
          faf95_max
        }
      }
    }
    clinvar_variants {
      variant_id
      clinical_significance
    }
  }
}

You can confirm that the ClinVar data returned from there is from a more recent release (2025-06-30).

This discrepancy between the browser/API should go away within a few days, if you need the most recent data right now, I would continue to use the API, and periodically check the BRCA1 page to see what the ClinVar release date there says (currently Apr 29, 2025).

Screenshot 2025-07-23 at 11.43.14
Screenshot 2025-07-23 at 11.43.141076×208 29.7 KB

Let us know if this makes sense, you need anything further, and thanks for your patience!

Best,

Riley

3

Hi Riley,
Got it. Thanks a lot for the quick response.

Regards,
Diya