Is SCN5A p.Pro614= (c.1842A>G) pathogenic?

SCN5A p.Pro614= (c.1842A>G) is classified Benign/Likely benign in SCN5A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-25). Very rare (popmax 0.00421%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with SCN5A p.Pro614= (c.1842A>G)?

SCN5A p.Pro614= (c.1842A>G) is associated with Cardiovascular phenotype, cardiac rhythm disease (ClinVar).

How common is SCN5A p.Pro614= (c.1842A>G) in the general population?

SCN5A p.Pro614= (c.1842A>G) is very rare (popmax 0.00421%, nfe) (gnomAD).

SCN5A p.Pro614=

c.1842A>G · rs766696979 · VCV201417

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00421%, nfe)

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 -3.2	GERP 0.18
Overall
CADD	4.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00421% European (non-Finnish) · 48/1,141,206 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00288%

Overall 0.00318% 49/1,539,274 alleles · very rare exomes 39/1,387,118 · genomes 10/152,156 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00421%	23,775
Admixed American	0.00196%	50,966

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.Pro614=
Coding: c.1842A>G
MANE Select: NM_000335
dbSNP: rs766696979
Type: single nucleotide variant
Location: chr3:38603760 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiac rhythm disease

Similar variants

SCN5A p.Pro614Ser Uncertain significance ★★ ⚠ same residue
SCN5A p.Pro614Thr 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-pro614 (accessed [today's date]).

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