TRPM2 p.Phe837=
c.2511C>T · VCV3771005
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0105%, nfe)
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 1.6 | GERP 0.46, phastCons 1 |
| Overall | ||
| CADD | 12.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0105%
European (non-Finnish) · 124/1,180,000 alleles
Filtering AF
0.00891%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00842%
Overall
0.00812%
131/1,613,354 alleles · ultra-rare
exomes 122/1,461,192 · genomes 9/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0105% | 9,516 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,831 |
| Admixed American | 0.00333% | 30,011 |
| African / African-American | 0.00133% | 75,034 |
| South Asian | 0.0011% | 91,076 |
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.Phe837=
- Coding
- c.2511C>T
- MANE Select
- NM_003307
- Type
- single nucleotide variant
- Location
- chr21:44401870 (GRCh38)
- Gene constraint
- LOEUF 1.047 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.51 · 15 PDB
- Residue 837
- an α-helix
Similar variants
- 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
- TRPM2 c.3549+8C>T Likely 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-phe837 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown