Is ANK2 p.Cys482Arg (c.1444T>C) pathogenic?

ANK2 p.Cys482Arg (c.1444T>C) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-03). AlphaMissense: likely pathogenic (0.9854); No allele count reported in gnomAD v4.1 (AN 1,568,764); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Cys482Arg (c.1444T>C)?

ANK2 p.Cys482Arg (c.1444T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Cys482Arg (c.1444T>C) in the general population?

ANK2 p.Cys482Arg (c.1444T>C) is no allele count reported in gnomAD v4.1 (AN 1,568,764) (gnomAD).

What do computational predictors say about ANK2 p.Cys482Arg (c.1444T>C)?

AlphaMissense predicts likely pathogenic (score 0.9854) — an in-silico prediction, not a clinical call.

ANK2 p.Cys482Arg

c.1444T>C · rs2493688240 · VCV1772779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9854 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,568,764)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9854	likely pathogenic · top 9% in ANK2
REVEL	0.537	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.26	donor gain, 41 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,568,764). 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.Cys482Arg
Coding: c.1444T>C
MANE Select: NM_001148
dbSNP: rs2493688240
Type: single nucleotide variant
Location: chr4:113264954 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 482: an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANK2 p.Cys482Ser Uncertain significance ★ same residue
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter 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 p.Ala1152Val 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-cys482arg (accessed [today's date]).

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