Is ANK2 p.Pro1747Arg (c.5240C>G) pathogenic?

ANK2 p.Pro1747Arg (c.5240C>G) is classified Likely benign in ANK2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.16); Rare (popmax 0.172%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Pro1747Arg (c.5240C>G)?

ANK2 p.Pro1747Arg (c.5240C>G) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Pro1747Arg (c.5240C>G) in the general population?

ANK2 p.Pro1747Arg (c.5240C>G) is rare (popmax 0.172%, amr) (gnomAD).

What do computational predictors say about ANK2 p.Pro1747Arg (c.5240C>G)?

AlphaMissense predicts likely benign (score 0.16) — an in-silico prediction, not a clinical call.

ANK2 p.Pro1747Arg

c.5240C>G · rs200628845 · VCV263614

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.16 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.172%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.16	likely benign
REVEL	0.14	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 0.82
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% Admixed American · 103/59,988 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.0116% 187/1,613,974 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.172%	582
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,644
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0128%	7,812
South Asian	0.011%	9,105
European (non-Finnish)	0.00398%	25,106

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.Pro1747Arg
Coding: c.5240C>G
dbSNP: rs200628845
Type: single nucleotide variant
Location: chr4:113353858 (GRCh38)

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

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-pro1747arg (accessed [today's date]).

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