TRPM2 p.Val460=
c.1380G>A · rs144644492 · VCV2652746
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.364%, mid)
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 4.2 | GERP -0.44, phastCons 1 |
| Overall | ||
| CADD | 10.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.364%
Middle Eastern · 22/6,044 alleles
Filtering AF
0.246%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.208%
Overall
0.0215%
347/1,614,130 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.364% | 275 |
| Ashkenazi Jewishnot grpmax-eligible | 0.216% | 463 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| European (non-Finnish) | 0.0191% | 5,245 |
| Admixed American | 0.0117% | 8,575 |
| African / African-American | 0.00933% | 10,721 |
| South Asian | 0.0011% | 91,080 |
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
- TRPM2
- Protein
- p.Val460=
- Coding
- c.1380G>A
- MANE Select
- NM_003307
- dbSNP
- rs144644492
- Type
- single nucleotide variant
- Location
- chr21:44390965 (GRCh38)
- Gene constraint
- LOEUF 1.047 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.51 · 15 PDB
- Residue 460
- an α-helix
Similar variants
- TRPC7 p.Glu460Asp Uncertain significance ★ ⚠ same residue
- TRPM2 c.1932+141G>A Benign ★★ same type
- TRPM2 c.1933-10T>C Benign ★★ same type
- TRPM2 c.2322-35T>C Benign ★★ same type
- TRPM2 c.2538+14C>T Benign ★★ same type
- TRPM2 c.2962+96A>G Benign ★★ same type
- TRPM2 c.3146+68T>C Benign ★★ same type
- TRPM2 c.3147-20T>C Benign ★★ 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/trpm2-p-val460 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown