Is SCN5A p.Ter2016= (c.6047G>A) pathogenic?

SCN5A p.Ter2016= (c.6047G>A) is classified Conflicting classifications of pathogenicity in SCN5A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-01-27). Very rare (popmax 0.00267%, sas); Associated with cardiac rhythm disease.

What condition is associated with SCN5A p.Ter2016= (c.6047G>A)?

SCN5A p.Ter2016= (c.6047G>A) is associated with cardiac rhythm disease (ClinVar).

How common is SCN5A p.Ter2016= (c.6047G>A) in the general population?

SCN5A p.Ter2016= (c.6047G>A) is very rare (popmax 0.00267%, sas) (gnomAD).

SCN5A p.Ter2016=

c.6047G>A · rs529885772 · VCV1171616

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, sas)

Conditions

cardiac rhythm disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.6, phastCons 1
Overall
CADD	9.386	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% South Asian · 2/74,952 alleles

Filtering AF 0.000447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000326%

Overall 0.000791% 12/1,516,582 alleles · very rare exomes 10/1,364,226 · genomes 2/152,356 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00267%	37,476
European (non-Finnish)	0.000883%	113,228

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.Ter2016=
Coding: c.6047G>A
MANE Select: NM_000335
dbSNP: rs529885772
Type: single nucleotide variant
Location: chr3:38550322 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.02 · 16 PDB
Residue 2016: the 'disordered' region

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.Ter2016Leu 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-ter2016 (accessed [today's date]).

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