Is SCN5A p.Val232= (c.696C>T) pathogenic?

SCN5A p.Val232= (c.696C>T) is classified Conflicting classifications of pathogenicity in SCN5A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-06). Ultra-rare (popmax 0.0187%, afr); Associated with Cardiovascular phenotype.

What condition is associated with SCN5A p.Val232= (c.696C>T)?

SCN5A p.Val232= (c.696C>T) is associated with Cardiovascular phenotype, cardiac rhythm disease (ClinVar).

How common is SCN5A p.Val232= (c.696C>T) in the general population?

SCN5A p.Val232= (c.696C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

SCN5A p.Val232=

c.696C>T · rs542346344 · VCV1540050

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

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 8.6	GERP 4.6, phastCons 1
Overall
CADD	10.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,836 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.000875% 14/1,600,084 alleles · ultra-rare exomes 2/1,447,726 · genomes 12/152,358 · joint denominator

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: SCN5A
Protein: p.Val232=
Coding: c.696C>T
MANE Select: NM_000335
dbSNP: rs542346344
Type: single nucleotide variant
Location: chr3:38613750 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.02 · 16 PDB
Residue 232: a UniProt-annotated variant site (in brgda1; uncertain significance); a β-strand

Full SCN5A 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

Also linked: cardiac rhythm disease

Similar variants

SCN5A p.Val232Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
SCN5A p.Val232Leu Uncertain significance ★ same residue
SCN5A c.1338+2T>A Pathogenic/Likely pathogenic ★★ same condition
SCN5A c.2263-2A>G Likely pathogenic ★★ same condition
SCN5A c.2437-1G>C Likely pathogenic ★★ same condition
SCN5A c.3508+1G>T Likely pathogenic ★★ same condition
SCN5A c.3509-1G>C Likely pathogenic ★★ same condition
SCN5A c.3837+1G>A Pathogenic ★★ 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/scn5a-p-val232 (accessed [today's date]).

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