GRM6 p.Cys244=
c.732T>C · rs777695214 · VCV1118906
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.247%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.48 | GERP -3.3, phastCons 0.88 |
| Overall | ||
| CADD | 8.482 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.247%
Middle Eastern · 15/6,080 alleles
Filtering AF
0.152%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.00434%
70/1,613,640 alleles · rare
exomes 63/1,461,732 · genomes 7/151,908 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.247% | 405 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,165 |
| African / African-American | 0.00535% | 18,704 |
| Admixed American | 0.00333% | 29,996 |
| South Asian | 0.00329% | 30,355 |
| European (non-Finnish) | 0.00263% | 38,060 |
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.Cys244=
- Coding
- c.732T>C
- MANE Select
- NM_000843
- dbSNP
- rs777695214
- Type
- single nucleotide variant
- Location
- chr5:178991549 (GRCh38)
- Gene constraint
- LOEUF 1.229 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.90 · 5 PDB
- Residue 244
- a disulfide bond
Similar variants
- GRM6 p.Cys244Tyr 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
- 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-cys244 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown