Is ANK2 p.Pro1762= (c.5286C>T) pathogenic?

ANK2 p.Pro1762= (c.5286C>T) is classified Likely benign in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-31). Very rare (popmax 0.00401%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Pro1762= (c.5286C>T)?

ANK2 p.Pro1762= (c.5286C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Pro1762= (c.5286C>T) in the general population?

ANK2 p.Pro1762= (c.5286C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

ANK2 p.Pro1762=

c.5286C>T · rs747998652 · VCV1746594

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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 0.13	GERP -0.13, phastCons 0.94
Overall
CADD	9.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,892 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,960 alleles · very rare exomes 1/1,461,822 · genomes 3/152,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,964
European (non-Finnish)	8.47e-05%	1,179,986

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.Pro1762=
Coding: c.5286C>T
MANE Select: NM_001148
dbSNP: rs747998652
Type: single nucleotide variant
Location: chr4:113353904 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1762: the 'disordered' 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.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
ANK2 p.Ala1214Thr 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-pro1762 (accessed [today's date]).

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