Is TRPM2 p.Arg1243= (c.3729G>C) pathogenic?

TRPM2 p.Arg1243= (c.3729G>C) is classified Likely benign in TRPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). Absent from gnomAD v4.1.

How common is TRPM2 p.Arg1243= (c.3729G>C) in the general population?

TRPM2 p.Arg1243= (c.3729G>C) is absent from gnomAD v4.1 (gnomAD).

TRPM2 p.Arg1243=

c.3729G>C · rs1012625878 · VCV2652755

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.18	GERP -2.6, phastCons 0.91
Overall
CADD	5.838	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRPM2
Protein: p.Arg1243=
Coding: c.3729G>C
MANE Select: NM_003307
dbSNP: rs1012625878
Type: single nucleotide variant
Location: chr21:44425761 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 15 PDB

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

Similar variants

TRPM2 p.Arg1243Gln Uncertain significance ★ ⚠ same residue
TRPM2 p.Arg1243Trp 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

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-arg1243 (accessed [today's date]).

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