Is ANK2 p.Pro632= (c.1896G>A) pathogenic?

ANK2 p.Pro632= (c.1896G>A) is classified Conflicting classifications of pathogenicity in ANK2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00802%, afr); Associated with cardiac arrhythmia, ankyrin-B-related.

What condition is associated with ANK2 p.Pro632= (c.1896G>A)?

ANK2 p.Pro632= (c.1896G>A) is associated with cardiac arrhythmia, ankyrin-B-related, long QT syndrome (ClinVar).

How common is ANK2 p.Pro632= (c.1896G>A) in the general population?

ANK2 p.Pro632= (c.1896G>A) is very rare (popmax 0.00802%, afr) (gnomAD).

How is Romano-Ward syndrome inherited?

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

ANK2 p.Pro632=

c.1896G>A · rs140761981 · VCV347311

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00802%, afr)

Conditions

cardiac arrhythmia, ankyrin-B-related

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 -1.8	GERP -4.9
Overall
CADD	6.166	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00802% African / African-American · 6/74,820 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00298% 48/1,612,414 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00802%	12,470
East Asian	0.00669%	14,959
Finnishnot grpmax-eligible	0.00626%	15,974
Admixed American	0.00334%	29,915
South Asian	0.0033%	30,281
Remaining individualsnot grpmax-eligible	0.0032%	31,217
European (non-Finnish)	0.00237%	42,112

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.Pro632=
Coding: c.1896G>A
MANE Select: NM_001148
dbSNP: rs140761981
Type: single nucleotide variant
Location: chr4:113282689 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 632: an α-helix

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.Pro632Leu Uncertain significance ★★ ⚠ 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
ANK2 c.2079+5T>G 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-pro632 (accessed [today's date]).

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