GRM6 p.Val304=
c.912C>T · rs1008360422 · VCV1135208
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0296%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -3.9 |
| Overall | ||
| CADD | 6.534 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0296%
East Asian · 13/43,974 alleles
Filtering AF
0.0174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0138%
Overall
0.00119%
19/1,598,098 alleles · ultra-rare
exomes 17/1,445,894 · genomes 2/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0296% | 3,383 |
| European (non-Finnish) | 0.000511% | 195,537 |
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
- GRM6
- Protein
- p.Val304=
- Coding
- c.912C>T
- MANE Select
- NM_000843
- dbSNP
- rs1008360422
- Type
- single nucleotide variant
- Location
- chr5:178990692 (GRCh38)
- Gene constraint
- LOEUF 1.229 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.90 · 5 PDB
Similar variants
- GRM6 c.722-2A>C Likely pathogenic ★★ same type
- GRM6 p.Arg238Ter Pathogenic ★★ same type
- GRM6 p.Arg446Ter Pathogenic ★★ same type
- GRM6 p.Arg621Ter Pathogenic ★★ same type
- GRM6 p.Gln488Ter Pathogenic ★★ same type
- GRM6 p.Gln681Ter Pathogenic/Likely pathogenic ★★ same type
- GRM6 p.Gln708Ter Pathogenic ★★ same type
- GRM6 p.Glu622Ter Pathogenic/Likely pathogenic ★★ 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/grm6-p-val304 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown