Is ANK2 p.Gln750Arg (c.2249A>G) pathogenic?

ANK2 p.Gln750Arg (c.2249A>G) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-11-02). AlphaMissense: likely benign (0.1006); Rare (popmax 0.174%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Gln750Arg (c.2249A>G)?

ANK2 p.Gln750Arg (c.2249A>G) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Gln750Arg (c.2249A>G) in the general population?

ANK2 p.Gln750Arg (c.2249A>G) is rare (popmax 0.174%, eas) (gnomAD).

What do computational predictors say about ANK2 p.Gln750Arg (c.2249A>G)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

ANK2 p.Gln750Arg

c.2249A>G · rs371787039 · VCV377473

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.174%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.283	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 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	25.1	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 0.174% East Asian · 78/44,846 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.00917% 148/1,613,968 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.174%	575
Remaining individualsnot grpmax-eligible	0.04%	2,500
South Asian	0.0307%	3,253
African / African-American	0.0147%	6,822
Admixed American	0.00167%	60,030
European (non-Finnish)	0.000424%	235,978

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.Gln750Arg
Coding: c.2249A>G
MANE Select: NM_001148
dbSNP: rs371787039
Type: single nucleotide variant
Location: chr4:113288458 (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.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
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-gln750arg (accessed [today's date]).

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