Is ANK2 p.Asp2377= (c.7131C>T) pathogenic?

ANK2 p.Asp2377= (c.7131C>T) is classified Likely benign in ANK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-03). Very rare (popmax 0.00935%, afr); Associated with long QT syndrome.

What condition is associated with ANK2 p.Asp2377= (c.7131C>T)?

ANK2 p.Asp2377= (c.7131C>T) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Asp2377= (c.7131C>T) in the general population?

ANK2 p.Asp2377= (c.7131C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

ANK2 p.Asp2377=

c.7131C>T · rs553324580 · VCV703648

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

long QT syndrome

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 -0.42	GERP -5.3
Overall
CADD	1.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,906 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00527% 85/1,613,942 alleles · very rare exomes 73/1,461,796 · genomes 12/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,701
South Asian	0.00769%	13,012
European (non-Finnish)	0.00559%	17,878
Remaining individualsnot grpmax-eligible	0.0048%	20,828
East Asian	0.00223%	44,880
Admixed American	0.00167%	59,992

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.Asp2377=
Coding: c.7131C>T
MANE Select: NM_001148
dbSNP: rs553324580
Type: single nucleotide variant
Location: chr4:113355749 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2377: the 'disordered' 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.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
ANK2 c.693+6G>A Uncertain significance ★★ same condition
ANK2 c.85-3C>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-asp2377 (accessed [today's date]).

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