Gnomad Genetics MCP Server

@cyanheads/gnomad-genetics-mcp-server Ancestry allele frequencies, LoF constraint, variant lists, and coverage from gnomAD, joined with ClinVar clinical significance via MCP. STDIO or Streamable HTTP. 8 Tools (+1 opt-in) • 2 Resources • 1 Prompt

Public Hosted Server: https://gnomad-genetics.caseyjhand.com/mcp

Overview

Population genetics over gnomAD (Broad Institute), with ClinVar clinical significance joined in from NCBI. Look up per-ancestry allele frequencies, gene loss-of-function constraint, gene variant catalogs, and sequencing coverage, then query large result sets with SQL.

Tools

Resources

All resource data is also reachable via tools. The list tools (gnomad_list_gene_variants, gnomad_get_coverage, gnomad_search_clinvar) return analytical row sets rather than stable single-URI documents, so they are not exposed as resources — call the tools instead.

Upstream-backed tools and resource reads share one fixed 45 s deadline across queue waits, retries, response bodies, and chained requests. A variant batch shares that deadline across every item: completed results remain available and unfinished primary items report upstream_timeout. Caller cancellation rejects the call.

Prompts

Datasets

dataset takes 14 values; reference_genome follows from it.

A subset keeps part of its parent release's samples (non_cancer leaves out cancer-study samples, non_ukb UK Biobank's) and can leave a callset unchanged: gnomad_r4_non_ukb genome counts equal gnomad_r4's, and gnomad_r2_1_non_cancer genome counts equal gnomad_r2_1's. No subset publishes joint exome + genome data, so its overall counts sum the carried callsets. gnomAD publishes no subset coverage or constraint, so gnomad_get_coverage and gnomad_get_gene_constraint read the parent release. A variant absent from a subset fails as variant_not_found, the same as one absent from gnomAD.

Capability reference

gnomad_get_variant tool

• Up to 25 IDs per call (raise via GNOMAD_MAX_VARIANT_BATCH), each a chrom-pos-ref-alt variantId on chromosome 1–22, X, or Y with an optional chr prefix (e.g. 1-55051215-G-GA) or an rsID (e.g. rs11591147). With GNOMAD_NORMALIZE_IDS on, an rsID is matched case-insensitively and a colon-separated ID (1:55039974:G:T, chr1:…) reads as 1-55039974-G-T; failed[].variant keeps the caller's spelling
• A bad or absent ID lands in failed[] as { variant, error, reason, recovery } without failing the rest; mitochondrial IDs (M, MT, chrM) fail as mitochondrial_unsupported, and an ambiguous rsID adds candidates. A coordinate ID carries no build: an absent one whose string also lifts over from the other build fails as variant_not_found_other_build, with the IDs it lifts to on the dataset's build in candidates. The lift is a hint — the server never rewrites or retries the ID — and costs one extra request per 25 absent coordinate IDs (one at the default batch cap), sent after the lookups and only when a coordinate ID came back absent; rsIDs are never lifted
• Returns the full per-ancestry frequency vector, the callset(s) carrying the variant, quality flags, consequence, predictor scores, and ClinVar significance. A validated population record survives ClinVar-only failure or expiry with clinvar: null and clinvar_unavailable: true
• On gnomad_r4, overall ac, an, af, and zygosity counts come from gnomAD's joint exome + genome data, whose an spans every callable sample in both callsets, even for a variant only one callset carries; joint_populations holds the same view per ancestry group. Every other dataset publishes no joint data (gnomad_r4_non_ukb and the other subsets, gnomad_r3, gnomad_r2_1, exac): it sums the carried callsets, a QC-failed callset included, and returns an empty joint_populations; callsets carries each one's own counts and filters. populations stays per callset, tagged by source
• callsets.exome and callsets.genome give each callset's own ac, an, af, zygosity counts, and QC filters (empty when that callset passed; the callset is null when it does not carry the variant). qc_status is pass when any callset carrying the variant passed, else filtered — gnomAD's browser rule. A filtered variant stays in found[]; its counts are low-confidence (AC0: no high-quality carrier)
• faf95 is gnomAD's filtering allele frequency (GroupMax FAF95: the lower bound of the 95% confidence interval of the AF of the ancestry group with the highest bound, over non-bottlenecked groups) as { value, group, source }, the figure to test against a disease threshold such as ACMG/AMP BA1 or BS1, which raw af is not. It reads gnomAD's joint value wherever a joint record exists (gnomad_r4), a null included, and otherwise the higher of the carried callsets' values, source naming which; each callsets.*.faf95 is that callset's own { value, group }. It is null when gnomAD reports none (AC 0, singletons, exac) and on gnomad_r4 and gnomad_r3 subsets, whose variant record carries the parent release's value rather than the subset's; a notice then names the parent. Read a subset's own value from faf95_max on gnomad_list_gene_variants, which gnomad_r4_non_ukb carries (gnomad_r3 subsets carry none)
• consequence is the most severe term across transcripts, as gnomAD shows it, and transcript_id the isoform it sits on. hgvsc, hgvsp, lof (LOFTEE's call: HC high-confidence, LC low-confidence, or OS other splice), lof_filter (e.g. END_TRUNC), and lof_flags (e.g. PHYLOCSF_WEAK) describe that transcript_id, each null when there is none. primary_transcript gives the term on that gene's MANE Select transcript (its canonical one where there is none, as on GRCh37), with is_mane_select, hgvsc, hgvsp, lof, lof_filter, and lof_flags: a stop_gained on a minor isoform can be a 3′ UTR change on the MANE transcript. It is null when the variant lies outside both transcripts, as on an exon only minor isoforms carry. It is read from the same reply, at no extra request
• lof_curations[] holds gnomAD's manual loss-of-function curations of the variant, each { gene_id, gene_symbol, verdict, flags, project }; it is empty for most variants, and a curation can overturn LOFTEE (a variant LOFTEE calls HC can carry a Not LoF verdict)
• Inspect each failed[].reason: only variant_not_found and variant_not_found_other_build report absence from the chosen dataset; timeouts and other failures leave presence unknown. On variant_not_found_other_build, settle the build first — retry with a candidate if the ID was written for the other build — then check gnomad_get_coverage before interpreting an absent variant. A l