GRM6 p.Ala648=
c.1944G>A · rs62638619 · VCV725523
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.142%, amr)
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 -9.6 | GERP -4.2 |
| Overall | ||
| CADD | 0.238 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.142%
Admixed American · 85/60,000 alleles
Filtering AF
0.117%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.108%
Overall
0.00756%
122/1,613,936 alleles · rare
exomes 112/1,461,602 · genomes 10/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.142% | 706 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,865 |
| African / African-American | 0.00799% | 12,510 |
| South Asian | 0.00659% | 15,176 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,246 |
| East Asian | 0.00223% | 44,870 |
| European (non-Finnish) | 0.00161% | 62,103 |
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.Ala648=
- Coding
- c.1944G>A
- MANE Select
- NM_000843
- dbSNP
- rs62638619
- Type
- single nucleotide variant
- Location
- chr5:178986310 (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.Ala648Thr Uncertain significance ★ ⚠ same residue
- GRM6 p.Ala648Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown