GRM4 p.Ser653=
c.1959G>A · rs34858760 · VCV788533
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 7.14%, 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 -10 | GERP -3.7 |
| Overall | ||
| CADD | 0.989 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.14%
African / African-American · 5,360/75,038 alleles
Filtering AF
6.98%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.92%
Overall
0.739%
11,936/1,614,160 alleles · common
exomes 8,422/1,461,836 · genomes 3,514/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.14% | 14 |
| Ashkenazi Jewishnot grpmax-eligible | 0.831% | 120 |
| Admixed American | 0.816% | 123 |
| Remaining individualsnot grpmax-eligible | 0.737% | 136 |
| Middle Eastern | 0.627% | 160 |
| European (non-Finnish) | 0.445% | 225 |
| South Asian | 0.0725% | 1,380 |
| Finnishnot grpmax-eligible | 0.0266% | 3,766 |
| East Asian | 0.00446% | 22,438 |
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.Ser653=
- Coding
- c.1959G>A
- MANE Select
- NM_000841
- dbSNP
- rs34858760
- Type
- single nucleotide variant
- Location
- chr6:34036151 (GRCh38)
- Gene constraint
- LOEUF 0.483 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 8 PDB
- Residue 653
- an α-helix
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-ser653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown