Is ANK2 p.Ala373= (c.1119G>A) pathogenic?

ANK2 p.Ala373= (c.1119G>A) is classified Likely benign in ANK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-09). Ultra-rare (popmax 0.02%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ala373= (c.1119G>A)?

ANK2 p.Ala373= (c.1119G>A) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is ANK2 p.Ala373= (c.1119G>A) in the general population?

ANK2 p.Ala373= (c.1119G>A) is ultra-rare (popmax 0.02%, afr) (gnomAD).

ANK2 p.Ala373=

c.1119G>A · rs139123934 · VCV413960

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

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 -3.4	GERP -4.9
Overall
CADD	7.378	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/75,042 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00987%

Overall 0.00248% 40/1,614,166 alleles · ultra-rare exomes 25/1,461,886 · genomes 15/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,003
Admixed American	0.0133%	7,502
South Asian	0.00769%	13,012
European (non-Finnish)	0.000847%	118,003

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.Ala373=
Coding: c.1119G>A
MANE Select: NM_001148
dbSNP: rs139123934
Type: single nucleotide variant
Location: chr4:113255863 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 373: an α-helix

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.Ala373Val Uncertain significance ★★ ⚠ same residue
ANK2 p.Ala373Thr Uncertain significance ★ 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

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-ala373 (accessed [today's date]).

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