Is ANK2 p.Ser3096Gly (c.9286A>G) pathogenic?

ANK2 p.Ser3096Gly (c.9286A>G) is classified Conflicting classifications of pathogenicity in ANK2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.148); Rare (popmax 0.821%, afr); Associated with long QT syndrome.

What condition is associated with ANK2 p.Ser3096Gly (c.9286A>G)?

ANK2 p.Ser3096Gly (c.9286A>G) is associated with long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Ser3096Gly (c.9286A>G) in the general population?

ANK2 p.Ser3096Gly (c.9286A>G) is rare (popmax 0.821%, afr) (gnomAD).

What do computational predictors say about ANK2 p.Ser3096Gly (c.9286A>G)?

AlphaMissense predicts likely benign (score 0.148) — an in-silico prediction, not a clinical call.

ANK2 p.Ser3096Gly

c.9286A>G · rs144158934 · VCV379629

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.148 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.821%, afr)

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.148	likely benign
REVEL	0.436	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.1	GERP 0.45, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	21.5	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 0.821% African / African-American · 616/75,042 alleles

Filtering AF 0.767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.746%

Overall 0.041% 661/1,614,086 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.821%	122
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed American	0.0167%	6,001
South Asian	0.011%	9,109
European (non-Finnish)	0.000254%	393,326

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.Ser3096Gly
Coding: c.9286A>G
MANE Select: NM_001148
dbSNP: rs144158934
Type: single nucleotide variant
Location: chr4:113357904 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3096: 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

Also linked: cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Ser3096= Likely benign ★ 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-ser3096gly (accessed [today's date]).

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