GRM6 p.Pro588=
c.1764G>A · rs138980304 · VCV1117960
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -1.4 | GERP -4.2 |
| Overall | ||
| CADD | 7.557 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,044 alleles
Filtering AF
0.00173%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.0023%
37/1,610,316 alleles · ultra-rare
exomes 35/1,458,148 · genomes 2/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,044 |
| Remaining individualsnot grpmax-eligible | 0.00803% | 12,459 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,510 |
| European (non-Finnish) | 0.00246% | 40,653 |
| East Asian | 0.00223% | 44,814 |
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.Pro588=
- Coding
- c.1764G>A
- MANE Select
- NM_000843
- dbSNP
- rs138980304
- Type
- single nucleotide variant
- Location
- chr5:178986490 (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.Pro588Leu Likely benign ★★ 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-pro588 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown