Is ANK2 p.Ile3285Thr (c.9854T>C) pathogenic?

ANK2 p.Ile3285Thr (c.9854T>C) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-07-01). AlphaMissense: likely pathogenic (0.7561); Low-frequency (popmax 3.27%, mid); Associated with atrial fibrillation.

What condition is associated with ANK2 p.Ile3285Thr (c.9854T>C)?

ANK2 p.Ile3285Thr (c.9854T>C) is associated with atrial fibrillation, long QT syndrome, cardiomyopathy (ClinVar).

How common is ANK2 p.Ile3285Thr (c.9854T>C) in the general population?

ANK2 p.Ile3285Thr (c.9854T>C) is low-frequency (popmax 3.27%, mid) (gnomAD).

What do computational predictors say about ANK2 p.Ile3285Thr (c.9854T>C)?

AlphaMissense predicts likely pathogenic (score 0.7561) — an in-silico prediction, not a clinical call.

ANK2 p.Ile3285Thr

c.9854T>C · rs36210417 · VCV190528

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

AlphaMissense

likely pathogenic

0.7561 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, mid)

Conditions

atrial fibrillation

Computational evidence

Protein change
AlphaMissense	0.7561	likely pathogenic
REVEL	0.541	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	23.9	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 3.27% Middle Eastern · 198/6,058 alleles

Filtering AF 2.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.75%

Overall 0.848% 13,687/1,614,066 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.27%	31
Ashkenazi Jewishnot grpmax-eligible	2.75%	36
Admixed American	1.08%	92
Remaining individualsnot grpmax-eligible	1.03%	97
European (non-Finnish)	0.886%	113
Finnishnot grpmax-eligible	0.57%	175
South Asian	0.491%	204
African / African-American	0.161%	620

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.Ile3285Thr
Coding: c.9854T>C
MANE Select: NM_001148
dbSNP: rs36210417
Type: single nucleotide variant
Location: chr4:113358472 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3285: the 'disordered' region

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

Disease context

atrial fibrillation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

ANK2 p.Ile3285= Likely benign ★★ same residue
ANK2 p.Ile3285Leu Conflicting classifications of pathogenicity ★ same residue
ANK2 p.Ile3285Met Uncertain significance ★ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 c.11032+11G>T Uncertain significance ★★ same condition
ANK2 c.11611-3T>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-ile3285thr (accessed [today's date]).

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