Is TRPM4 p.Ala808= (c.2424G>A) pathogenic?

TRPM4 p.Ala808= (c.2424G>A) is classified Likely benign in TRPM4 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-26). Very rare (popmax 0.000348%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TRPM4 p.Ala808= (c.2424G>A)?

TRPM4 p.Ala808= (c.2424G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is TRPM4 p.Ala808= (c.2424G>A) in the general population?

TRPM4 p.Ala808= (c.2424G>A) is very rare (popmax 0.000348%, nfe) (gnomAD).

TRPM4 p.Ala808=

c.2424G>A · rs2514178986 · VCV1791061

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000348%, nfe)

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 -0.2
Overall
CADD	5.177	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000348% European (non-Finnish) · 4/1,149,640 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000287% 4/1,394,302 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.Ala808=
Coding: c.2424G>A
MANE Select: NM_017636
dbSNP: rs2514178986
Type: single nucleotide variant
Location: chr19:49196653 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 42 PDB
Residue 808: a β-strand

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.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
TRPM4 c.2953+5G>A Uncertain significance ★★ same condition
TRPM4 p.Ala1001Val 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-ala808 (accessed [today's date]).

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