Is SCN5A p.Pro609= (c.1827A>G) pathogenic?

SCN5A p.Pro609= (c.1827A>G) is classified Likely benign in SCN5A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-01). Absent from gnomAD v4.1; Associated with cardiac rhythm disease.

What condition is associated with SCN5A p.Pro609= (c.1827A>G)?

SCN5A p.Pro609= (c.1827A>G) is associated with cardiac rhythm disease (ClinVar).

How common is SCN5A p.Pro609= (c.1827A>G) in the general population?

SCN5A p.Pro609= (c.1827A>G) is absent from gnomAD v4.1 (gnomAD).

SCN5A p.Pro609=

c.1827A>G · rs2471746361 · VCV1780861

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cardiac rhythm disease

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 -6.5	GERP -8.3
Overall
CADD	0.119	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.Pro609=
Coding: c.1827A>G
MANE Select: NM_000335
dbSNP: rs2471746361
Type: single nucleotide variant
Location: chr3:38603775 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.02 · 16 PDB

Full SCN5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiac rhythm disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCN5A p.Pro609Leu 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.3508+1G>T Likely pathogenic ★★ same condition
SCN5A c.3837+1G>A Pathogenic ★★ same condition
SCN5A c.4242+1G>C Pathogenic/Likely pathogenic ★★ same condition
SCN5A c.611+1G>A Pathogenic ★★ same condition
SCN5A c.934+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-pro609 (accessed [today's date]).

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