Is SCN5A p.Trp1439fs (c.4313dup) pathogenic?

SCN5A p.Trp1439fs (c.4313dup) is classified Pathogenic in SCN5A (ClinVar, No assertion criteria, 1 submitter). No gnomAD frequency available for this variant; Associated with Brugada syndrome.

What condition is associated with SCN5A p.Trp1439fs (c.4313dup)?

SCN5A p.Trp1439fs (c.4313dup) is associated with Brugada syndrome (ClinVar).

How common is SCN5A p.Trp1439fs (c.4313dup) in the general population?

SCN5A p.Trp1439fs (c.4313dup) is no gnomAD frequency available for this variant (gnomAD).

How is Brugada syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SCN5A p.Trp1439fs

c.4313dup · rs2125835486 · VCV1299249

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 25 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.13	GERP 0.85, phastCons 0.93

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: SCN5A
Protein: p.Trp1439fs
Coding: c.4313dup
MANE Select: NM_000335
dbSNP: rs2125835486
Type: Duplication
Location: chr3:38556561 (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

Brugada syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Brugada syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SCN5A c.3954_3960+1dup Likely pathogenic ★★ same condition
SCN5A p.Gly1844fs Likely pathogenic ★★ same condition
SCN5A p.Ile723fs Pathogenic ★★ same condition
SCN5A p.Leu813fs Pathogenic ★★ same condition
SCN5A p.Trp1439Ter Pathogenic ★ same residue
SCN5A p.Leu1935fs Uncertain significance ★ same condition
SCN5A p.Trp1439Arg Uncertain significance ★ ⚠ same residue
SCN5A c.1338+2T>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-trp1439fs (accessed [today's date]).

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