Is ANK2 p.Ala1085= (c.3255G>T) pathogenic?

ANK2 p.Ala1085= (c.3255G>T) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0594%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ala1085= (c.3255G>T)?

ANK2 p.Ala1085= (c.3255G>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Ala1085= (c.3255G>T) in the general population?

ANK2 p.Ala1085= (c.3255G>T) is ultra-rare (popmax 0.0594%, nfe) (gnomAD).

ANK2 p.Ala1085=

c.3255G>T · rs56173868 · VCV219766

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0594%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.9	GERP -1.6
Overall
CADD	4.524	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0594% European (non-Finnish) · 701/1,180,012 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.0866% 1,398/1,614,092 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.837%	119
Ashkenazi Jewishnot grpmax-eligible	0.328%	305
Remaining individualsnot grpmax-eligible	0.088%	1,136
European (non-Finnish)grpmax	0.0594%	1,683
Admixed American	0.01%	10,001
African / African-American	0.004%	25,001

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala1085=
Coding: c.3255G>T
MANE Select: NM_001148
dbSNP: rs56173868
Type: single nucleotide variant
Location: chr4:113333084 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1085: the zu5 1 domain; the 'interaction with sptbn1' 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-ala1085 (accessed [today's date]).

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