Is ANK2 p.Asp923Val (c.2768A>T) pathogenic?

ANK2 p.Asp923Val (c.2768A>T) is classified Uncertain significance in ANK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-10). AlphaMissense: likely benign (0.241); Absent from gnomAD v4.1; Associated with cardiac arrhythmia, ankyrin-B-related.

What condition is associated with ANK2 p.Asp923Val (c.2768A>T)?

ANK2 p.Asp923Val (c.2768A>T) is associated with cardiac arrhythmia, ankyrin-B-related, long QT syndrome (ClinVar).

How common is ANK2 p.Asp923Val (c.2768A>T) in the general population?

ANK2 p.Asp923Val (c.2768A>T) is absent from gnomAD v4.1 (gnomAD).

How is Romano-Ward syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ANK2 p.Asp923Val (c.2768A>T)?

AlphaMissense predicts likely benign (score 0.241) — an in-silico prediction, not a clinical call.

ANK2 p.Asp923Val

c.2768A>T · rs2083706279 · VCV1357507

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.241 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

cardiac arrhythmia, ankyrin-B-related

Computational evidence

Protein change
AlphaMissense	0.241	likely benign
REVEL	0.251	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	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANK2
Protein: p.Asp923Val
Coding: c.2768A>T
MANE Select: NM_001148
dbSNP: rs2083706279
Type: single nucleotide variant
Location: chr4:113317781 (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

cardiac arrhythmia, ankyrin-B-related — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome

For Romano-Ward syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ANK2 p.Asp923Gly Uncertain significance ★ ⚠ same residue
ANK2 p.Asp923= 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 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-asp923val (accessed [today's date]).

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