Is ANK2 p.Val1095fs (c.3281dup) pathogenic?

ANK2 p.Val1095fs (c.3281dup) is classified Pathogenic in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). No gnomAD frequency available for this variant; Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Val1095fs (c.3281dup)?

ANK2 p.Val1095fs (c.3281dup) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Val1095fs (c.3281dup) in the general population?

ANK2 p.Val1095fs (c.3281dup) is no gnomAD frequency available for this variant (gnomAD).

ANK2 p.Val1095fs

c.3281dup · rs2502650416 · VCV1729746

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

Conditions

Cardiovascular phenotype

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 29 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 2.4, 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: ANK2
Protein: p.Val1095fs
Coding: c.3281dup
MANE Select: NM_001148
dbSNP: rs2502650416
Type: Duplication
Location: chr4:113333109 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1095: a β-strand; the zu5 1 domain; the 'interaction with sptbn1' region

Full ANK2 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

Similar variants

ANK2 p.Val1095= Likely benign ★ same residue
ANK2 p.Glu1100Ter Pathogenic ★ same condition
ANK2 c.2685_2693+30dup Uncertain significance ★ same condition
ANK2 p.Glu2268_Thr2269insSerThrLysThrGlu Likely benign ★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 p.Gln3921Ter 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-val1095fs (accessed [today's date]).

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