Is SCN5A p.Ser519fs (c.1555del) pathogenic?

SCN5A p.Ser519fs (c.1555del) is classified Pathogenic in SCN5A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-29). No gnomAD frequency available for this variant.

How common is SCN5A p.Ser519fs (c.1555del) in the general population?

SCN5A p.Ser519fs (c.1555del) is no gnomAD frequency available for this variant (gnomAD).

SCN5A p.Ser519fs

c.1555del · rs2125901794 · VCV1455694

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 3.7, phastCons 1

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.Ser519fs
Coding: c.1555del
MANE Select: NM_000335
dbSNP: rs2125901794
Type: Deletion
Location: chr3:38604047 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.02 · 16 PDB
Residue 519: the 'disordered' region

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

Similar variants

SCN5A p.Ser519= Likely benign ★★ same residue
SCN5A p.Ser519Phe Uncertain significance ★ same residue
SCN5A p.Ser519Pro Uncertain significance ★ ⚠ same residue
SCN5A c.3961-2_3961del Pathogenic/Likely pathogenic ★★ same type
SCN5A c.4243-2del Pathogenic/Likely pathogenic ★★ same type
SCN5A c.4296+1del Pathogenic/Likely pathogenic ★★ same type
SCN5A p.Ala606fs Pathogenic/Likely pathogenic ★★ same type
SCN5A p.Arg14fs Pathogenic ★★ same type

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-ser519fs (accessed [today's date]).

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