GRM2 p.Ile140=
c.420T>C · rs779977094 · VCV754238
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00341%, amr)
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 -3.9 | GERP -3.9 |
| Overall | ||
| CADD | 5.27 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00341%
Admixed American · 2/58,614 alleles
Filtering AF
0.000566%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000212%
Overall
0.000127%
2/1,570,510 alleles · very rare
exomes 2/1,418,378 · genomes 0/152,132 · joint denominator
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
- GRM2
- Protein
- p.Ile140=
- Coding
- c.420T>C
- MANE Select
- NM_000839
- dbSNP
- rs779977094
- Type
- single nucleotide variant
- Location
- chr3:51709403 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.17 · 31 PDB
- Residue 140
- a β-strand
Similar variants
- GRM2 p.Asn824= Benign ★★ same type
- GRM2 p.Ala127Glu Uncertain significance ★ ⚠ same type
- GRM2 p.Ala275Val Uncertain significance ★ same type
- GRM2 p.Ala281Val Uncertain significance ★ ⚠ same type
- GRM2 p.Ala287Val Uncertain significance ★ ⚠ same type
- GRM2 p.Ala363Thr Uncertain significance ★ ⚠ same type
- GRM2 p.Ala430Val Uncertain significance ★ same type
- GRM2 p.Ala47Val 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/grm2-p-ile140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown