Is ANK2 p.Arg1817fs (c.5450_5451del) pathogenic?

ANK2 p.Arg1817fs (c.54505451del) is classified Pathogenic in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). Associated with ANK2-associated seizure disorder.

What condition is associated with ANK2 p.Arg1817fs (c.5450_5451del)?

ANK2 p.Arg1817fs (c.5450_5451del) is associated with ANK2-associated seizure disorder (ClinVar).

ANK2 p.Arg1817fs

c.5450_5451del · VCV4683080

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ANK2-associated seizure disorder

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 5.7	GERP 2.8, phastCons 0.77

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

Variant & gene context

Gene: ANK2
Protein: p.Arg1817fs
Coding: c.5450_5451del
MANE Select: NM_001148
Type: Microsatellite
Location: chr4:113354063 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1817: the 'disordered' region; the 'repeat-rich region' region

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

Disease context

ANK2-associated seizure disorder

Similar variants

ANK2 p.Asn2047fs Likely pathogenic same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg888Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Gly3456fs Pathogenic/Likely pathogenic ★★ same condition
ANK2 c.85-28508A>G Uncertain significance ★★ same condition
ANK2 c.85-57022A>C Uncertain significance ★★ same condition
ANK2 p.Ala41Thr Uncertain significance ★★ ⚠ same condition
ANK2 p.Gln2672His Uncertain significance ★★ ⚠ 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-arg1817fs (accessed [today's date]).

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