GRM8 p.Ala686=
c.2058G>A · rs756180003 · VCV751119
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 -11 | GERP -5.8 |
| Overall | ||
| CADD | 0.755 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,936 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.00093%
15/1,613,410 alleles · very rare
exomes 12/1,461,558 · genomes 3/151,852 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,968 |
| South Asian | 0.0033% | 30,345 |
| East Asian | 0.00223% | 44,856 |
| African / African-American | 0.00134% | 74,812 |
| European (non-Finnish) | 0.000678% | 147,475 |
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
- GRM8
- Protein
- p.Ala686=
- Coding
- c.2058G>A
- MANE Select
- NM_000845
- dbSNP
- rs756180003
- Type
- single nucleotide variant
- Location
- chr7:126533324 (GRCh38)
- Gene constraint
- LOEUF 0.687 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.11 · 10 PDB
Similar variants
- GRM8 c.1495-9T>C Benign ★★ same type
- GRM8 p.Arg561= Benign ★★ same type
- GRM8 p.Gly231= Benign ★★ same type
- GRM8 p.His32Gln Benign ★★ same type
- GRM8 p.Ile265Thr Benign ★★ same type
- GRM8 p.Ile488= Benign ★★ same type
- GRM8 p.Phe119= Benign ★★ same type
- GRM8 p.Phe21Cys Benign ★★ 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/grm8-p-ala686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown