Is TRPM4 p.Arg969Pro (c.2906_2907delinsCC) pathogenic?

TRPM4 p.Arg969Pro (c.29062907delinsCC) is classified Uncertain significance in TRPM4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). No gnomAD frequency available for this variant; Associated with progressive familial heart block type IB.

What condition is associated with TRPM4 p.Arg969Pro (c.2906_2907delinsCC)?

TRPM4 p.Arg969Pro (c.2906_2907delinsCC) is associated with progressive familial heart block type IB (ClinVar).

How common is TRPM4 p.Arg969Pro (c.2906_2907delinsCC) in the general population?

TRPM4 p.Arg969Pro (c.2906_2907delinsCC) is no gnomAD frequency available for this variant (gnomAD).

TRPM4 p.Arg969Pro

Q: How is Hereditary progressive cardiac conduction defect inherited?

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

c.2906_2907delinsCC · rs2514204381 · VCV2041915

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 9.5	phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 43 kb · p 0.93 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Arg969Pro
Coding: c.2906_2907delinsCC
MANE Select: NM_017636
dbSNP: rs2514204381
Type: Indel
Location: chr19:49200738 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 42 PDB
Residue 969: an α-helix

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.Arg969His Uncertain significance ★★ ⚠ same residue
TRPM4 p.Leu951fs Uncertain significance ★★ same condition
TRPM4 p.Ser560Lys Uncertain significance ★★ same condition
TRPM4 p.Arg1094Pro Uncertain significance ★ same condition
TRPM4 p.Arg969Cys Uncertain significance ★ ⚠ same residue
TRPM4 p.Arg969Leu Uncertain significance ★ ⚠ same residue
TRPM4 p.Cys758_Cys759delinsTrpGly Uncertain significance ★ same condition
TRPM4 p.Lys1140_Arg1141delinsAsnTrp 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-arg969pro (accessed [today's date]).

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