Is ANK2 p.Arg982Gln (c.2945G>A) pathogenic?

ANK2 p.Arg982Gln (c.2945G>A) is classified Uncertain significance in ANK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). AlphaMissense: likely pathogenic (0.9432); Ultra-rare (popmax 0.0125%, nfe); Associated with long QT syndrome.

What condition is associated with ANK2 p.Arg982Gln (c.2945G>A)?

ANK2 p.Arg982Gln (c.2945G>A) is associated with long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Arg982Gln (c.2945G>A) in the general population?

ANK2 p.Arg982Gln (c.2945G>A) is ultra-rare (popmax 0.0125%, nfe) (gnomAD).

What do computational predictors say about ANK2 p.Arg982Gln (c.2945G>A)?

AlphaMissense predicts likely pathogenic (score 0.9432) — an in-silico prediction, not a clinical call.

ANK2 p.Arg982Gln

c.2945G>A · rs769214999 · VCV238575

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9432 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, nfe)

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.9432	likely pathogenic
REVEL	0.607	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	31.0	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 0.0125% European (non-Finnish) · 147/1,180,026 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00942% 152/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0125%	8,027
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00133%	74,932
South Asian	0.0011%	91,082

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.Arg982Gln
Coding: c.2945G>A
MANE Select: NM_001148
dbSNP: rs769214999
Type: single nucleotide variant
Location: chr4:113330290 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 982: a β-strand; 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

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Arg982Gly Uncertain significance ★ same residue
ANK2 p.Arg982Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter 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-arg982gln (accessed [today's date]).

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