Is ANK2 p.Thr3152Ala (c.9454A>G) pathogenic?

ANK2 p.Thr3152Ala (c.9454A>G) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0661); Low-frequency (popmax 1.09%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Thr3152Ala (c.9454A>G)?

ANK2 p.Thr3152Ala (c.9454A>G) is associated with Cardiovascular phenotype, long QT syndrome, dilated cardiomyopathy (ClinVar).

How common is ANK2 p.Thr3152Ala (c.9454A>G) in the general population?

ANK2 p.Thr3152Ala (c.9454A>G) is low-frequency (popmax 1.09%, afr) (gnomAD).

What do computational predictors say about ANK2 p.Thr3152Ala (c.9454A>G)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

ANK2 p.Thr3152Ala

c.9454A>G · rs61741040 · VCV191562

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.136	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -5.7
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% African / African-American · 819/75,056 alleles

Filtering AF 1.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 1%

Overall 0.059% 953/1,614,114 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.09%	92
Admixed American	0.105%	953
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0592%	1,689
South Asian	0.00329%	30,362
European (non-Finnish)	0.0022%	45,384

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.Thr3152Ala
Coding: c.9454A>G
MANE Select: NM_001148
dbSNP: rs61741040
Type: single nucleotide variant
Location: chr4:113358072 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3152: the 'disordered' 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 dilated cardiomyopathy cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Thr3152Asn 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 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

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-thr3152ala (accessed [today's date]).

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