Is ANK2 p.Ser874= (c.2622A>G) pathogenic?

ANK2 p.Ser874= (c.2622A>G) is classified Conflicting classifications of pathogenicity in ANK2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-21). Ultra-rare (popmax 0.0211%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ser874= (c.2622A>G)?

ANK2 p.Ser874= (c.2622A>G) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Ser874= (c.2622A>G) in the general population?

ANK2 p.Ser874= (c.2622A>G) is ultra-rare (popmax 0.0211%, nfe) (gnomAD).

ANK2 p.Ser874=

c.2622A>G · rs764486532 · VCV238574

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, nfe)

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 -8.9	GERP -5
Overall
CADD	0.629	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0211% European (non-Finnish) · 249/1,180,012 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0181%

Overall 0.0158% 255/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0211%	4,739
Remaining individualsnot grpmax-eligible	0.0048%	20,828
African / African-American	0.004%	24,973

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.Ser874=
Coding: c.2622A>G
MANE Select: NM_001148
dbSNP: rs764486532
Type: single nucleotide variant
Location: chr4:113311328 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 874: a modified residue (phosphoserine)

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-ser874 (accessed [today's date]).

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