GRM1 p.Asp474=
c.1422C>T · rs371221115 · VCV752759
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -0.53 | phastCons 0.1 |
| Overall | ||
| CADD | 10.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00335%
54/1,613,542 alleles · ultra-rare
exomes 49/1,461,394 · genomes 5/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.00668% | 14,979 |
| Admixed American | 0.00667% | 15,001 |
| South Asian | 0.0055% | 18,197 |
| European (non-Finnish) | 0.00314% | 31,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
| Finnishnot grpmax-eligible | 0.00156% | 64,002 |
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
- GRM1
- Protein
- p.Asp474=
- Coding
- c.1422C>T
- MANE Select
- NM_001278064
- dbSNP
- rs371221115
- Type
- single nucleotide variant
- Location
- chr6:146352485 (GRCh38)
- Gene constraint
- LOEUF 0.417 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.38 · 8 PDB
- Residue 474
- an α-helix
Similar variants
- GRM1 c.2661-7309A>T Uncertain significance ★★ same type
- GRM1 c.951-6T>A Uncertain significance ★★ same type
- GRM1 p.Ala1005Thr Uncertain significance ★★ ⚠ same type
- GRM1 p.Ala11Gly Uncertain significance ★★ ⚠ same type
- GRM1 p.Ala883Ser Uncertain significance ★★ ⚠ same type
- GRM1 p.Ala91Val Uncertain significance ★★ ⚠ same type
- GRM1 p.Arg1185Gln Uncertain significance ★★ ⚠ same type
- GRM1 p.Arg358Lys 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/grm1-p-asp474 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown