Is ANK2 p.Lys2091= (c.6273A>G) pathogenic?

ANK2 p.Lys2091= (c.6273A>G) is classified Likely benign in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-09). Ultra-rare (popmax 0.0165%, mid); Associated with long QT syndrome.

What condition is associated with ANK2 p.Lys2091= (c.6273A>G)?

ANK2 p.Lys2091= (c.6273A>G) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Lys2091= (c.6273A>G) in the general population?

ANK2 p.Lys2091= (c.6273A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ANK2 p.Lys2091=

c.6273A>G · rs2154022097 · VCV1108789

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

long QT syndrome

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 3.5	GERP -1, phastCons 0.065
Overall
CADD	2.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000124% 2/1,614,118 alleles · ultra-rare exomes 2/1,461,842 · genomes 0/152,276 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Lys2091=
Coding: c.6273A>G
MANE Select: NM_001148
dbSNP: rs2154022097
Type: single nucleotide variant
Location: chr4:113354891 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2091: the 'disordered' 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

Similar variants

ANK2 p.Lys2091Arg Likely benign ★ same residue
ANK2 p.Arg3113Ter 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
ANK2 c.3125+6G>A Uncertain significance ★★ same condition
ANK2 c.693+6G>A 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-lys2091 (accessed [today's date]).

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