GRM7 p.Pro694=
c.2082C>G · rs147672583 · VCV1959596
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0813%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 11.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0813%
African / African-American · 61/75,026 alleles
Filtering AF
0.0649%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.059%
Overall
0.00446%
72/1,614,098 alleles · ultra-rare
exomes 38/1,461,828 · genomes 34/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0813% | 1,230 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| South Asian | 0.00329% | 30,361 |
| European (non-Finnish) | 8.47e-05% | 1,179,981 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- GRM7
- Protein
- p.Pro694=
- Coding
- c.2082C>G
- MANE Select
- NM_000844
- dbSNP
- rs147672583
- Type
- single nucleotide variant
- Location
- chr3:7578988 (GRCh38)
- Gene constraint
- LOEUF 0.549 · pLI 0.37 (gnomAD)
- Structure
- AlphaFold pLDDT 84.48 · 12 PDB
- Residue 694
- a UniProt-annotated variant site (in nedshba; does not rescue axon outgrowth defects when expressed in a heterologous system); a UniProt-annotated variant site (in nedshba)
Similar variants
- GRM7 p.Ala29Thr Uncertain significance ★★ ⚠ same type
- GRM7 p.Arg493His Uncertain significance ★★ ⚠ same type
- GRM7 p.Arg614Cys Uncertain significance ★★ ⚠ same type
- GRM7 p.Arg9His Uncertain significance ★★ ⚠ same type
- GRM7 p.Asn505Ser Uncertain significance ★★ ⚠ same type
- GRM7 p.Cys770Ser Uncertain significance ★★ ⚠ same type
- GRM7 p.Glu140Gln Uncertain significance ★★ ⚠ same type
- GRM7 p.Glu501Lys Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/grm7-p-pro694 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown