Is ANK2 p.Arg3568Trp (c.10702C>T) pathogenic?

ANK2 p.Arg3568Trp (c.10702C>T) is classified Conflicting classifications of pathogenicity in ANK2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1596); Rare (popmax 0.116%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Arg3568Trp (c.10702C>T)?

ANK2 p.Arg3568Trp (c.10702C>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Arg3568Trp (c.10702C>T) in the general population?

ANK2 p.Arg3568Trp (c.10702C>T) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about ANK2 p.Arg3568Trp (c.10702C>T)?

AlphaMissense predicts likely benign (score 0.1596) — an in-silico prediction, not a clinical call.

ANK2 p.Arg3568Trp

c.10702C>T · rs72556376 · VCV190574

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1596 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1596	likely benign
REVEL	0.578	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.8, phastCons 0.92
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	26.6	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 0.116% Middle Eastern · 7/6,054 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0122% 197/1,612,676 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	865
Admixed American	0.0368%	2,721
Remaining individualsnot grpmax-eligible	0.016%	6,241
European (non-Finnish)	0.0124%	8,077
African / African-American	0.00934%	10,708
South Asian	0.0055%	18,195

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.Arg3568Trp
Coding: c.10702C>T
MANE Select: NM_001148
dbSNP: rs72556376
Type: single nucleotide variant
Location: chr4:113360843 (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

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

Also linked: long QT syndrome cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Arg3568Gln Conflicting classifications of pathogenicity ★ same residue
ANK2 p.Arg3568= Likely benign ★ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11032+11G>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-arg3568trp (accessed [today's date]).

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