Is ANK2 p.Glu1309= (c.3927A>G) pathogenic?

ANK2 p.Glu1309= (c.3927A>G) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-09). Rare (popmax 0.539%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Glu1309= (c.3927A>G)?

ANK2 p.Glu1309= (c.3927A>G) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Glu1309= (c.3927A>G) in the general population?

ANK2 p.Glu1309= (c.3927A>G) is rare (popmax 0.539%, sas) (gnomAD).

ANK2 p.Glu1309=

c.3927A>G · rs567570285 · VCV347320

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.539%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.084	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -5.3, phastCons 0.99
Overall
CADD	5.953	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.539% South Asian · 491/91,086 alleles

Filtering AF 0.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.484%

Overall 0.0326% 527/1,614,148 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.539%	186
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Middle Eastern	0.0165%	6,060
Admixed American	0.005%	20,009
African / African-American	0.00133%	75,036
European (non-Finnish)	0.000169%	590,009

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.Glu1309=
Coding: c.3927A>G
MANE Select: NM_001148
dbSNP: rs567570285
Type: single nucleotide variant
Location: chr4:113341721 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1309: an α-helix; the 'upa domain' 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 cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11032+11G>T Uncertain significance ★★ same condition
ANK2 c.11611-3T>A Uncertain significance ★★ same condition
ANK2 c.1783-3C>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-glu1309 (accessed [today's date]).

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