Is ANK2 p.Arg1013= (c.3037A>C) pathogenic?

ANK2 p.Arg1013= (c.3037A>C) is classified Likely benign in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). Ultra-rare (popmax 0.0164%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Arg1013= (c.3037A>C)?

ANK2 p.Arg1013= (c.3037A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Arg1013= (c.3037A>C) in the general population?

ANK2 p.Arg1013= (c.3037A>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ANK2 p.Arg1013=

c.3037A>C · VCV3864079

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.199	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -4.9, phastCons 0.2
Overall
CADD	8.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,144 alleles · ultra-rare exomes 4/1,461,882 · genomes 1/152,262 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.000339%	295,015

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.Arg1013=
Coding: c.3037A>C
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113330382 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1013: 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

Similar variants

ANK2 p.Arg1013Ter Uncertain significance ★ same residue
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter 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 p.Ala1152Val 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-arg1013 (accessed [today's date]).

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