GRM1 p.Val520=
c.1560G>C · rs989543701 · VCV2991393
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
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 -2.9 | |
| Overall | ||
| CADD | 0.244 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,994 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000929%
15/1,613,970 alleles · very rare
exomes 11/1,461,752 · genomes 4/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,999 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| European (non-Finnish) | 0.000847% | 117,994 |
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.Val520=
- Coding
- c.1560G>C
- MANE Select
- NM_001278064
- dbSNP
- rs989543701
- Type
- single nucleotide variant
- Location
- chr6:146357652 (GRCh38)
- Gene constraint
- LOEUF 0.417 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.38 · 8 PDB
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-val520 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown