Is TRPM2 p.Val602Ala (c.1805T>C) pathogenic?

TRPM2 p.Val602Ala (c.1805T>C) is classified Benign/Likely benign in TRPM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-01). AlphaMissense: likely benign (0.1252); Low-frequency (popmax 1.07%, mid).

How common is TRPM2 p.Val602Ala (c.1805T>C) in the general population?

TRPM2 p.Val602Ala (c.1805T>C) is low-frequency (popmax 1.07%, mid) (gnomAD).

What do computational predictors say about TRPM2 p.Val602Ala (c.1805T>C)?

AlphaMissense predicts likely benign (score 0.1252) — an in-silico prediction, not a clinical call.

TRPM2 p.Val602Ala

c.1805T>C · rs149930126 · VCV778911

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1252 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1252	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.049	GERP -0.9, phastCons 0.77
Regional constraint	o/e 1.01	unconstrained · MANE · 88 kb · p 0.67 · regional, not allelic
Overall
CADD	15.72	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.07% Middle Eastern · 65/6,058 alleles

Filtering AF 0.864% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.788%

Overall 0.0492% 793/1,612,382 alleles · low-frequency exomes 585/1,460,386 · genomes 208/151,996 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.07%	93
African / African-American	0.363%	276
Remaining individualsnot grpmax-eligible	0.106%	947
Admixed American	0.0767%	1,304
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
South Asian	0.0549%	1,821
European (non-Finnish)	0.0231%	4,322
Finnishnot grpmax-eligible	0.0016%	62,666

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.Val602Ala
Coding: c.1805T>C
MANE Select: NM_003307
dbSNP: rs149930126
Type: single nucleotide variant
Location: chr21:44395424 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 15 PDB
Residue 602: a β-strand

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

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-val602ala (accessed [today's date]).

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