GRM6 p.Ala24=
c.72G>A · rs191142743 · VCV769676
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 6.6%, amr) — too common for a highly-penetrant pathogenic allele
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 -0.6 | GERP -0.43 |
| Overall | ||
| CADD | 10.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.6%
Admixed American · 1,673/25,348 alleles
Filtering AF
6.34%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.23%
Overall
0.235%
2,828/1,205,688 alleles · common
exomes 1,875/1,055,576 · genomes 953/150,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 6.6% | 15 |
| East Asian | 1.84% | 54 |
| Remaining individualsnot grpmax-eligible | 0.368% | 272 |
| South Asian | 0.174% | 576 |
| African / African-American | 0.142% | 702 |
| Middle Eastern | 0.135% | 739 |
| European (non-Finnish) | 0.0397% | 2,517 |
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.Ala24=
- Coding
- c.72G>A
- MANE Select
- NM_000843
- dbSNP
- rs191142743
- Type
- single nucleotide variant
- Location
- chr5:178994873 (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-ala24 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown