Is ANK2 p.Val1928= (c.5784A>C) pathogenic?

ANK2 p.Val1928= (c.5784A>C) is classified Likely benign in ANK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-03). Ultra-rare (popmax 0.0233%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Val1928= (c.5784A>C)?

ANK2 p.Val1928= (c.5784A>C) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is ANK2 p.Val1928= (c.5784A>C) in the general population?

ANK2 p.Val1928= (c.5784A>C) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

ANK2 p.Val1928=

c.5784A>C · rs757420275 · VCV413962

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.76	GERP -5.7
Overall
CADD	1.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% Admixed American · 14/59,998 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00446% 72/1,614,024 alleles · ultra-rare exomes 60/1,461,806 · genomes 12/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)	0.00398%	25,106
African / African-American	0.00133%	74,940

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.Val1928=
Coding: c.5784A>C
MANE Select: NM_001148
dbSNP: rs757420275
Type: single nucleotide variant
Location: chr4:113354402 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1928: the 'disordered' region; the 'repeat-rich region' region

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

Similar variants

ANK2 p.Val1928Ala Uncertain significance ★ ⚠ same residue
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11611-3T>A Uncertain significance ★★ same condition
ANK2 c.1783-3C>T Uncertain significance ★★ same condition
ANK2 c.2079+5T>G Uncertain significance ★★ same condition
ANK2 c.2278-3C>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-val1928 (accessed [today's date]).

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