Is ANK2 p.Arg3454fs (c.10360del) pathogenic?

ANK2 p.Arg3454fs (c.10360del) is classified Likely pathogenic in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with ANK2 p.Arg3454fs (c.10360del)?

ANK2 p.Arg3454fs (c.10360del) is associated with Inborn genetic diseases (ClinVar).

How common is ANK2 p.Arg3454fs (c.10360del) in the general population?

ANK2 p.Arg3454fs (c.10360del) is absent from gnomAD (gnomAD).

ANK2 p.Arg3454fs

c.10360del · rs2096016231 · VCV985206

Likely pathogenic Single submitter

Classification

Likely 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

Inborn genetic diseases

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 4.5	GERP 2.6, 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: ANK2
Protein: p.Arg3454fs
Coding: c.10360del
MANE Select: NM_001148
dbSNP: rs2096016231
Type: Deletion
Location: chr4:113358978 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3454: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANK2 p.Arg3454Ser Likely benign ★★ same residue
ANK2 p.Arg3454Lys Uncertain significance ★ same residue
ANK2 p.Arg3454= Likely benign ★ same residue
ANK2 p.Arg1098Cys Uncertain significance ★★ same condition
ANK2 c.2179-1G>A Likely pathogenic ★ same condition
ANK2 p.Arg3642Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
ANK2 p.Gly3912Ser Uncertain significance ★ same condition
ANK2 p.Gly3456fs Pathogenic/Likely 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/ank2-p-arg3454fs (accessed [today's date]).

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