GRM6 p.Val193=
c.579G>A · rs1274655234 · VCV1496325
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.062 | GERP 0.1, phastCons 0.84 |
| Overall | ||
| CADD | 14.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,026 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000496%
8/1,614,148 alleles · very rare
exomes 8/1,461,828 · genomes 0/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,013 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,500 |
| European (non-Finnish) | 0.000424% | 236,003 |
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.Val193=
- Coding
- c.579G>A
- MANE Select
- NM_000843
- dbSNP
- rs1274655234
- Type
- single nucleotide variant
- Location
- chr5:178992009 (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 p.Val193fs Pathogenic ★ same residue
- 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
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-val193 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown