Is ANK2 p.Ser3495fs (c.10483_10486del) pathogenic?

ANK2 p.Ser3495fs (c.1048310486del) is classified Pathogenic in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). Very rare (popmax 8.47e-05%, nfe); Associated with long QT syndrome.

What condition is associated with ANK2 p.Ser3495fs (c.10483_10486del)?

ANK2 p.Ser3495fs (c.10483_10486del) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Ser3495fs (c.10483_10486del) in the general population?

ANK2 p.Ser3495fs (c.10483_10486del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ANK2 p.Ser3495fs

c.10483_10486del · rs1564067737 · VCV570614

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

long QT 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 38 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.79	GERP -5.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,944 alleles

Overall 6.2e-05% 1/1,614,072 alleles · very rare exomes 1/1,461,728 · genomes 0/152,344 · joint denominator

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: ANK2
Protein: p.Ser3495fs
Coding: c.10483_10486del
MANE Select: NM_001148
dbSNP: rs1564067737
Type: Deletion
Location: chr4:113359098 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full ANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

ANK2 c.2901-3del Uncertain significance ★★ same condition
ANK2 c.11032+19_11032+20del Benign/Likely benign ★★ same condition
ANK2 p.Asp3081fs Pathogenic ★ same condition
ANK2 p.Glu1091fs Pathogenic ★ same condition
ANK2 p.Leu3108fs Pathogenic ★ same condition
ANK2 p.Phe3055fs Pathogenic ★ same condition
ANK2 p.Ser3273fs Pathogenic ★ same condition
ANK2 p.Ser930fs 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/ank2-p-ser3495fs (accessed [today's date]).

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