Is TRPM4 p.Pro4= (c.12G>C) pathogenic?

TRPM4 p.Pro4= (c.12G>C) is classified Likely benign in TRPM4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-09). Very rare (popmax 0.00119%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TRPM4 p.Pro4= (c.12G>C)?

TRPM4 p.Pro4= (c.12G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is TRPM4 p.Pro4= (c.12G>C) in the general population?

TRPM4 p.Pro4= (c.12G>C) is very rare (popmax 0.00119%, sas) (gnomAD).

TRPM4 p.Pro4=

c.12G>C · rs1403043676 · VCV1769371

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Conditions

Cardiovascular phenotype

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 -1.5
Overall
CADD	5.784	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/83,978 alleles

Overall 7.23e-05% 1/1,382,716 alleles · very rare

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: TRPM4
Protein: p.Pro4=
Coding: c.12G>C
MANE Select: NM_017636
dbSNP: rs1403043676
Type: single nucleotide variant
Location: chr19:49157878 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 42 PDB

Full TRPM4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPM4 p.Pro4Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TRPM4 p.Pro4Arg Uncertain significance ★★ ⚠ same residue
TRPM4 p.Ile376Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRPM4 c.1050+1G>A Uncertain significance ★★ same condition
TRPM4 c.1150+5A>T Uncertain significance ★★ same condition
TRPM4 c.2019+5G>A Uncertain significance ★★ same condition
TRPM4 c.2645+1G>A Uncertain significance ★★ same condition
TRPM4 c.2953+1G>A Uncertain significance ★★ same condition

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/trpm4-p-pro4 (accessed [today's date]).

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