Is ANK2 p.Ser232Cys (c.694A>T) pathogenic?

ANK2 p.Ser232Cys (c.694A>T) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely pathogenic (0.9762); Absent from gnomAD v4.1; Associated with long QT syndrome.

What condition is associated with ANK2 p.Ser232Cys (c.694A>T)?

ANK2 p.Ser232Cys (c.694A>T) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Ser232Cys (c.694A>T) in the general population?

ANK2 p.Ser232Cys (c.694A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK2 p.Ser232Cys (c.694A>T)?

AlphaMissense predicts likely pathogenic (score 0.9762) — an in-silico prediction, not a clinical call.

ANK2 p.Ser232Cys

c.694A>T · VCV3721452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9762 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.9762	likely pathogenic
REVEL	0.664	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 24 kb · p 3.4e-14 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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.Ser232Cys
Coding: c.694A>T
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113240485 (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.Ser232Gly Uncertain significance ★ same residue
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

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-ser232cys (accessed [today's date]).

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