GRM6 p.Pro431=
c.1293G>A · rs371275499 · VCV1583263
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0307%, 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 -20 | GERP -4.2 |
| Overall | ||
| CADD | 0.074 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0307%
African / African-American · 23/74,928 alleles
Filtering AF
0.021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0178%
Overall
0.00279%
45/1,613,926 alleles · ultra-rare
exomes 27/1,461,750 · genomes 18/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0307% | 3,258 |
| Middle Eastern | 0.0165% | 6,072 |
| East Asian | 0.0111% | 8,974 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| Admixed American | 0.00167% | 59,994 |
| European (non-Finnish) | 0.000932% | 107,270 |
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.Pro431=
- Coding
- c.1293G>A
- MANE Select
- NM_000843
- dbSNP
- rs371275499
- Type
- single nucleotide variant
- Location
- chr5:178988996 (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.Pro431Leu Uncertain significance ★★ ⚠ same residue
- GRM6 p.Pro431Ser Uncertain significance ★★ ⚠ same residue
- GRM6 p.Pro431Thr Uncertain significance ★ ⚠ 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
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-pro431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown