Is ANK2 p.Cys3636Arg (c.10906T>C) pathogenic?

ANK2 p.Cys3636Arg (c.10906T>C) is classified Uncertain significance in ANK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-13). AlphaMissense: likely pathogenic (0.6864); Very rare (popmax 8.48e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Cys3636Arg (c.10906T>C)?

ANK2 p.Cys3636Arg (c.10906T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Cys3636Arg (c.10906T>C) in the general population?

ANK2 p.Cys3636Arg (c.10906T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ANK2 p.Cys3636Arg (c.10906T>C)?

AlphaMissense predicts likely pathogenic (score 0.6864) — an in-silico prediction, not a clinical call.

ANK2 p.Cys3636Arg

c.10906T>C · rs2154052758 · VCV2500529

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6864	likely pathogenic
REVEL	0.606	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,842 alleles

Overall 6.84e-05% 1/1,461,626 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANK2
Protein: p.Cys3636Arg
Coding: c.10906T>C
MANE Select: NM_001148
dbSNP: rs2154052758
Type: single nucleotide variant
Location: chr4:113365056 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3636: an α-helix; the death 2 domain

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.Cys3636Tyr 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-cys3636arg (accessed [today's date]).

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