Is ANK2 p.Ile1078Val (c.3232A>G) pathogenic?

ANK2 p.Ile1078Val (c.3232A>G) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.1291); Very rare (popmax 6.84e-05%); Associated with long QT syndrome.

What condition is associated with ANK2 p.Ile1078Val (c.3232A>G)?

ANK2 p.Ile1078Val (c.3232A>G) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Ile1078Val (c.3232A>G) in the general population?

ANK2 p.Ile1078Val (c.3232A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ANK2 p.Ile1078Val (c.3232A>G)?

AlphaMissense predicts likely benign (score 0.1291) — an in-silico prediction, not a clinical call.

ANK2 p.Ile1078Val

c.3232A>G · rs1269748001 · VCV2914818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1291 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.1291	likely benign
REVEL	0.249	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 6.2	GERP 2.4, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	23.6	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 6.84e-05%

Overall 6.84e-05% 1/1,461,878 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.Ile1078Val
Coding: c.3232A>G
MANE Select: NM_001148
dbSNP: rs1269748001
Type: single nucleotide variant
Location: chr4:113333061 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1078: a β-strand; the zu5 1 domain; the 'interaction with sptbn1' region

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.Ile1078= Likely benign ★★ same residue
ANK2 p.Ile1078Leu Uncertain significance ★ 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

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-ile1078val (accessed [today's date]).

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