Is ANK2 p.Asp1384= (c.4152T>C) pathogenic?

ANK2 p.Asp1384= (c.4152T>C) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-01). Rare (popmax 0.834%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Asp1384= (c.4152T>C)?

ANK2 p.Asp1384= (c.4152T>C) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Asp1384= (c.4152T>C) in the general population?

ANK2 p.Asp1384= (c.4152T>C) is rare (popmax 0.834%, afr) (gnomAD).

ANK2 p.Asp1384=

c.4152T>C · rs116128106 · VCV238580

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.834%, 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 -1.3	GERP -5.8, phastCons 0.001
Overall
CADD	1.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.834% African / African-American · 626/75,056 alleles

Filtering AF 0.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.758%

Overall 0.082% 1,324/1,614,048 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.834%	120
South Asian	0.411%	244
Middle Eastern	0.347%	288
Remaining individualsnot grpmax-eligible	0.118%	845
Admixed American	0.112%	896
European (non-Finnish)	0.0135%	7,421
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,865

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.Asp1384=
Coding: c.4152T>C
MANE Select: NM_001148
dbSNP: rs116128106
Type: single nucleotide variant
Location: chr4:113343046 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1384: a β-strand; 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-asp1384 (accessed [today's date]).

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