Is ANK2 p.Lys726= (c.2178G>A) pathogenic?

ANK2 p.Lys726= (c.2178G>A) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-07). Absent from gnomAD v4.1; Associated with long QT syndrome.

What condition is associated with ANK2 p.Lys726= (c.2178G>A)?

ANK2 p.Lys726= (c.2178G>A) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Lys726= (c.2178G>A) in the general population?

ANK2 p.Lys726= (c.2178G>A) is absent from gnomAD v4.1 (gnomAD).

ANK2 p.Lys726=

c.2178G>A · rs2065381346 · VCV1024282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	donor loss · deltas
Pangolin	Δ0.39	loss · gain 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.8	GERP 2.5, phastCons 1
Overall
CADD	22.1	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.Lys726=
Coding: c.2178G>A
MANE Select: NM_001148
dbSNP: rs2065381346
Type: single nucleotide variant
Location: chr4:113287703 (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 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 c.11611-3T>A Uncertain significance ★★ same condition
ANK2 c.1783-3C>T Uncertain significance ★★ same condition
ANK2 c.2079+5T>G Uncertain significance ★★ same condition
ANK2 c.2278-3C>T Uncertain significance ★★ same condition
ANK2 c.3125+6G>A Uncertain significance ★★ same condition
ANK2 c.693+6G>A Uncertain significance ★★ same condition
ANK2 c.85-3C>T 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-lys726 (accessed [today's date]).

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