Is ANK2 p.Ala3339= (c.10017G>A) pathogenic?

ANK2 p.Ala3339= (c.10017G>A) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-10). Rare (popmax 0.148%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ala3339= (c.10017G>A)?

ANK2 p.Ala3339= (c.10017G>A) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is ANK2 p.Ala3339= (c.10017G>A) in the general population?

ANK2 p.Ala3339= (c.10017G>A) is rare (popmax 0.148%, mid) (gnomAD).

ANK2 p.Ala3339=

c.10017G>A · rs774143296 · VCV391280

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -5.1, phastCons 0.037
Overall
CADD	2.606	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,078 alleles

Filtering AF 0.0772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0577%

Overall 0.0159% 257/1,612,010 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	675
Remaining individualsnot grpmax-eligible	0.0224%	4,459
European (non-Finnish)	0.0181%	5,511
South Asian	0.0154%	6,497
African / African-American	0.00539%	18,564
East Asian	0.00223%	44,776
Admixed American	0.00167%	59,818

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.Ala3339=
Coding: c.10017G>A
MANE Select: NM_001148
dbSNP: rs774143296
Type: single nucleotide variant
Location: chr4:113358635 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3339: the 'disordered' region

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

Similar variants

ANK2 p.Ala3339Val Conflicting classifications of pathogenicity ★ ⚠ 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 c.2278-3C>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-ala3339 (accessed [today's date]).

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