Is ANK2 p.Arg1011= (c.3033C>T) pathogenic?

ANK2 p.Arg1011= (c.3033C>T) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-26). Ultra-rare (popmax 0.066%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Arg1011= (c.3033C>T)?

ANK2 p.Arg1011= (c.3033C>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Arg1011= (c.3033C>T) in the general population?

ANK2 p.Arg1011= (c.3033C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

ANK2 p.Arg1011=

c.3033C>T · rs142052072 · VCV238576

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.082	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.1, phastCons 1
Overall
CADD	10.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.0159% 257/1,614,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
European (non-Finnish)	0.0199%	5,021
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00666%	15,004
Finnishnot grpmax-eligible	0.00468%	21,349
African / African-American	0.00266%	37,531
East Asian	0.00223%	44,890
South Asian	0.0011%	91,086

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.Arg1011=
Coding: c.3033C>T
MANE Select: NM_001148
dbSNP: rs142052072
Type: single nucleotide variant
Location: chr4:113330378 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1011: the zu5 1 domain; the 'interaction with sptbn1' 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.Arg1011Cys Uncertain significance ★ same residue
ANK2 p.Arg1011Ser Uncertain significance ★ same residue
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

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-arg1011 (accessed [today's date]).

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