Is ANK2 p.Pro1823= (c.5469C>T) pathogenic?

ANK2 p.Pro1823= (c.5469C>T) is classified Benign in ANK2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 13.1%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Pro1823= (c.5469C>T)?

ANK2 p.Pro1823= (c.5469C>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

ANK2 p.Pro1823=

Q: How common is ANK2 p.Pro1823= (c.5469C>T) in the general population?

ANK2 p.Pro1823= (c.5469C>T) is common (popmax 13.1%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5469C>T · rs33966911 · VCV257580

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 13.1%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.3	GERP -4.6
Overall
CADD	0.994	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.1% Middle Eastern · 792/6,058 alleles

Filtering AF 12.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 12%

Overall 9.59% 154,812/1,613,984 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	13.1%	8
Ashkenazi Jewishnot grpmax-eligible	11.4%	9
European (non-Finnish)	11%	9
Finnishnot grpmax-eligible	10.3%	10
Remaining individualsnot grpmax-eligible	9.38%	11
Admixed American	5.98%	17
Amishnot grpmax-eligible	4.93%	20
South Asian	3.03%	33
African / African-American	1.9%	53
East Asian	0.0334%	2,991

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.Pro1823=
Coding: c.5469C>T
MANE Select: NM_001148
dbSNP: rs33966911
Type: single nucleotide variant
Location: chr4:113354087 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1823: 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 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-pro1823 (accessed [today's date]).

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