Is SCN5A p.Pro576= (c.1728C>T) pathogenic?

SCN5A p.Pro576= (c.1728C>T) is classified Likely benign in SCN5A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-09). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with SCN5A p.Pro576= (c.1728C>T)?

SCN5A p.Pro576= (c.1728C>T) is associated with Cardiovascular phenotype, cardiac rhythm disease (ClinVar).

How common is SCN5A p.Pro576= (c.1728C>T) in the general population?

SCN5A p.Pro576= (c.1728C>T) is absent from gnomAD v4.1 (gnomAD).

SCN5A p.Pro576=

c.1728C>T · rs1575800832 · VCV753857

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1.9	GERP -0.088, phastCons 0.98
Overall
CADD	2.184	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SCN5A
Protein: p.Pro576=
Coding: c.1728C>T
MANE Select: NM_000335
dbSNP: rs1575800832
Type: single nucleotide variant
Location: chr3:38603874 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.02 · 16 PDB
Residue 576: the 'disordered' region

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.Pro576Ala 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
SCN5A c.3960+1G>A Pathogenic/Likely 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-pro576 (accessed [today's date]).

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