Is ANK2 p.Ile3603Val (c.10807A>G) pathogenic?

ANK2 p.Ile3603Val (c.10807A>G) is classified Uncertain significance in ANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-04). AlphaMissense: likely benign (0.0838); Very rare (popmax 0.00178%, nfe); Associated with long QT syndrome.

What condition is associated with ANK2 p.Ile3603Val (c.10807A>G)?

ANK2 p.Ile3603Val (c.10807A>G) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Ile3603Val (c.10807A>G) in the general population?

ANK2 p.Ile3603Val (c.10807A>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about ANK2 p.Ile3603Val (c.10807A>G)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

ANK2 p.Ile3603Val

c.10807A>G · rs1057521529 · VCV383148

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.195	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.74, phastCons 0.97
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	15.06	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,684 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00143% 23/1,613,406 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,175
Remaining individualsnot grpmax-eligible	0.0016%	62,448
African / African-American	0.00134%	74,900

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.Ile3603Val
Coding: c.10807A>G
MANE Select: NM_001148
dbSNP: rs1057521529
Type: single nucleotide variant
Location: chr4:113363388 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3603: an α-helix; the death 2 domain

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.Ile3603= Likely benign ★★ 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-ile3603val (accessed [today's date]).

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