Is ANK2 p.Arg1582Gln (c.4745G>A) pathogenic?

ANK2 p.Arg1582Gln (c.4745G>A) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0677); Rare (popmax 0.164%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Arg1582Gln (c.4745G>A)?

ANK2 p.Arg1582Gln (c.4745G>A) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Arg1582Gln (c.4745G>A) in the general population?

ANK2 p.Arg1582Gln (c.4745G>A) is rare (popmax 0.164%, nfe) (gnomAD).

What do computational predictors say about ANK2 p.Arg1582Gln (c.4745G>A)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

ANK2 p.Arg1582Gln

c.4745G>A · rs138842207 · VCV191535

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.164%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.037	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -2, phastCons 0.89
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	2.647	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 0.164% European (non-Finnish) · 1,936/1,179,936 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.155%

Overall 0.125% 2,023/1,614,020 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.164%	609
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Admixed American	0.0267%	3,751
Finnishnot grpmax-eligible	0.0266%	3,766
African / African-American	0.02%	5,002
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.0022%	45,533

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.Arg1582Gln
Coding: c.4745G>A
MANE Select: NM_001148
dbSNP: rs138842207
Type: single nucleotide variant
Location: chr4:113353363 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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.Arg1582Trp Benign/Likely benign ★★ same residue
ANK2 p.Arg1582= Likely benign ★ 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-arg1582gln (accessed [today's date]).

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