GRM4 p.Pro647=
c.1941C>T · rs138247081 · VCV738471
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.18%, afr)
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 -8.8 | GERP -3.7 |
| Overall | ||
| CADD | 0.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.18%
African / African-American · 135/74,948 alleles
Filtering AF
0.155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.146%
Overall
0.0107%
172/1,614,082 alleles · rare
exomes 102/1,461,828 · genomes 70/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.18% | 555 |
| East Asian | 0.0134% | 7,483 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,925 |
| South Asian | 0.0022% | 45,542 |
| European (non-Finnish) | 0.00169% | 59,001 |
| Admixed American | 0.00167% | 60,014 |
| Finnishnot grpmax-eligible | 0.00156% | 64,036 |
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
- GRM4
- Protein
- p.Pro647=
- Coding
- c.1941C>T
- MANE Select
- NM_000841
- dbSNP
- rs138247081
- Type
- single nucleotide variant
- Location
- chr6:34036169 (GRCh38)
- Gene constraint
- LOEUF 0.483 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 8 PDB
Similar variants
- GRM4 p.Ala251Thr Uncertain significance ★ ⚠ same type
- GRM4 p.Ala278Thr Uncertain significance ★ ⚠ same type
- GRM4 p.Ala399Thr Uncertain significance ★ ⚠ same type
- GRM4 p.Ala422Thr Uncertain significance ★ ⚠ same type
- GRM4 p.Ala701Thr Uncertain significance ★ ⚠ same type
- GRM4 p.Ala81Thr Uncertain significance ★ ⚠ same type
- GRM4 p.Ala862Val Uncertain significance ★ ⚠ same type
- GRM4 p.Ala885Thr Uncertain significance ★ ⚠ 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/grm4-p-pro647 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown