Is ANK2 p.Thr3093Pro (c.9277A>C) pathogenic?

ANK2 p.Thr3093Pro (c.9277A>C) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: ambiguous (0.4622); Very rare (popmax 0.00167%, amr).

How common is ANK2 p.Thr3093Pro (c.9277A>C) in the general population?

ANK2 p.Thr3093Pro (c.9277A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ANK2 p.Thr3093Pro (c.9277A>C)?

AlphaMissense predicts ambiguous (score 0.4622) — an in-silico prediction, not a clinical call.

ANK2 p.Thr3093Pro

c.9277A>C · VCV3360965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4622 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.4622	ambiguous
REVEL	0.926	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	25.3	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 0.00167% Admixed American · 1/60,018 alleles

Overall 0.000657% 1/152,286 alleles · very rare

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.Thr3093Pro
Coding: c.9277A>C
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113357895 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3093: the 'disordered' region

Full ANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANK2 p.Thr3093= Conflicting classifications of pathogenicity ★ same residue
ANK2 p.Thr3093Asn Uncertain significance ★ ⚠ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same type
ANK2 p.Arg1088Ter Pathogenic ★★ same type
ANK2 p.Arg3113Ter Pathogenic ★★ same type
ANK2 p.Arg888Ter Pathogenic/Likely pathogenic ★★ same type
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same type
ANK2 p.Arg977Ter Pathogenic ★★ same type

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-thr3093pro (accessed [today's date]).

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