Is ANK2 p.Ser2422= (c.7266C>T) pathogenic?

ANK2 p.Ser2422= (c.7266C>T) is classified Conflicting classifications of pathogenicity in ANK2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.0213%, afr); Associated with long QT syndrome.

What condition is associated with ANK2 p.Ser2422= (c.7266C>T)?

ANK2 p.Ser2422= (c.7266C>T) is associated with long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Ser2422= (c.7266C>T) in the general population?

ANK2 p.Ser2422= (c.7266C>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

ANK2 p.Ser2422=

c.7266C>T · rs150349588 · VCV516922

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.51	GERP -3.3, phastCons 0.025
Overall
CADD	7.463	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/75,038 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0145% 234/1,614,066 alleles · ultra-rare exomes 219/1,461,806 · genomes 15/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,690
European (non-Finnish)	0.0175%	5,728
Remaining individualsnot grpmax-eligible	0.0128%	7,814
Admixed American	0.00667%	15,002

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.Ser2422=
Coding: c.7266C>T
MANE Select: NM_001148
dbSNP: rs150349588
Type: single nucleotide variant
Location: chr4:113355884 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Also linked: cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Ser2422Asn Conflicting classifications of pathogenicity ★ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter 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
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-ser2422 (accessed [today's date]).

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