Is TRPM2 p.Val131= (c.393C>T) pathogenic?

TRPM2 p.Val131= (c.393C>T) is classified Likely benign in TRPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-25). Very rare (popmax 0.00133%, afr).

How common is TRPM2 p.Val131= (c.393C>T) in the general population?

TRPM2 p.Val131= (c.393C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

TRPM2 p.Val131=

c.393C>T · rs1251309612 · VCV735922

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 -0.34	GERP -3.2, phastCons 0.043
Overall
CADD	1.126	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,944 alleles

Overall 6.2e-05% 1/1,614,098 alleles · very rare exomes 0/1,461,852 · genomes 1/152,246 · 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: TRPM2
Protein: p.Val131=
Coding: c.393C>T
MANE Select: NM_003307
dbSNP: rs1251309612
Type: single nucleotide variant
Location: chr21:44364252 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 15 PDB
Residue 131: a β-strand

Full TRPM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPM2 p.Val131Ile 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-val131 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown