Is ANK2 p.Lys1457= (c.4371G>A) pathogenic?

ANK2 p.Lys1457= (c.4371G>A) is classified Likely pathogenic in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Absent from gnomAD v4.1; Associated with ANK2-associated disorder.

What condition is associated with ANK2 p.Lys1457= (c.4371G>A)?

ANK2 p.Lys1457= (c.4371G>A) is associated with ANK2-associated disorder (ClinVar).

How common is ANK2 p.Lys1457= (c.4371G>A) in the general population?

ANK2 p.Lys1457= (c.4371G>A) is absent from gnomAD v4.1 (gnomAD).

ANK2 p.Lys1457=

c.4371G>A · VCV4071958

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ANK2-associated disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.801	moderately pathogenic-leaning
Splicing
SpliceAI	Δ0.80	donor loss · deltas
Pangolin	Δ0.84	loss · gain 0.72 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANK2
Protein: p.Lys1457=
Coding: c.4371G>A
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113346022 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1457: the death 1 domain; the 'disordered' region

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

Disease context

ANK2-associated disorder

Similar variants

ANK2 p.Lys1457Glu Uncertain significance ★★ same residue
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg888Ter 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
ANK2 p.Lys114Glu 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-lys1457 (accessed [today's date]).

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