Is TRPM4 p.Val749= (c.2247C>T) pathogenic?

TRPM4 p.Val749= (c.2247C>T) is classified Likely benign in TRPM4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). No allele count reported in gnomAD v4.1 (AN 1,555,358); Associated with progressive familial heart block type IB.

What condition is associated with TRPM4 p.Val749= (c.2247C>T)?

TRPM4 p.Val749= (c.2247C>T) is associated with progressive familial heart block type IB (ClinVar).

How common is TRPM4 p.Val749= (c.2247C>T) in the general population?

TRPM4 p.Val749= (c.2247C>T) is no allele count reported in gnomAD v4.1 (AN 1,555,358) (gnomAD).

TRPM4 p.Val749=

Q: How is Hereditary progressive cardiac conduction defect inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2247C>T · rs1309839953 · VCV796493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,555,358)

Conditions

progressive familial heart block type IB

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 -0.043
Overall
CADD	1.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,555,358). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRPM4
Protein: p.Val749=
Coding: c.2247C>T
MANE Select: NM_017636
dbSNP: rs1309839953
Type: single nucleotide variant
Location: chr19:49196476 (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

progressive familial heart block type IB — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary progressive cardiac conduction defect (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

TRPM4 p.Val749Ile Uncertain significance ★★ ⚠ same residue
TRPM4 p.Val749Phe Uncertain significance ★ ⚠ same residue
TRPM4 p.Ile1040Thr Pathogenic/Likely pathogenic ★★ same condition
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.1150+6A>G Uncertain significance ★★ same condition
TRPM4 c.1263+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-val749 (accessed [today's date]).

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