Is ANK2 p.Pro1052= (c.3156A>G) pathogenic?

ANK2 p.Pro1052= (c.3156A>G) is classified Likely benign in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-06). Ultra-rare (popmax 0.0134%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Pro1052= (c.3156A>G)?

ANK2 p.Pro1052= (c.3156A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Pro1052= (c.3156A>G) in the general population?

ANK2 p.Pro1052= (c.3156A>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

ANK2 p.Pro1052=

c.3156A>G · rs776369900 · VCV1728234

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

Cardiovascular phenotype

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 5.3	GERP -1.7, phastCons 1
Overall
CADD	12.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,878 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,613,962 alleles · ultra-rare exomes 6/1,461,850 · genomes 0/152,112 · joint denominator

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.Pro1052=
Coding: c.3156A>G
MANE Select: NM_001148
dbSNP: rs776369900
Type: single nucleotide variant
Location: chr4:113332002 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1052: 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.Pro1052Arg Uncertain significance ★★ same residue
ANK2 p.Pro1052Gln Uncertain significance ★ same residue
ANK2 p.Pro1052Ser 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

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-pro1052 (accessed [today's date]).

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