GRM6 p.Ala652=
c.1956C>T · rs62638621 · VCV99639
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 5.05%, afr) — 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 -0.036 | GERP -4.2, phastCons 0.11 |
| Overall | ||
| CADD | 3.308 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.05%
African / African-American · 3,792/75,058 alleles
Filtering AF
4.92%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.86%
Overall
0.269%
4,349/1,614,050 alleles · common
exomes 2,214/1,461,698 · genomes 2,135/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.05% | 20 |
| Remaining individualsnot grpmax-eligible | 0.323% | 309 |
| Middle Eastern | 0.313% | 319 |
| Admixed American | 0.3% | 333 |
| European (non-Finnish) | 0.0123% | 8,138 |
| South Asian | 0.0121% | 8,279 |
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.Ala652=
- Coding
- c.1956C>T
- MANE Select
- NM_000843
- dbSNP
- rs62638621
- Type
- single nucleotide variant
- Location
- chr5:178986298 (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.Ala652Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- GRM6 p.Ala652Val 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
- GRM6 p.Gln681Ter 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-ala652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown