Is CDK2AP2 p.Thr75Ala (c.223A>G) pathogenic?

CDK2AP2 p.Thr75Ala (c.223A>G) is classified Uncertain significance in CDK2AP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.0937); Absent from gnomAD v4.1.

How common is CDK2AP2 p.Thr75Ala (c.223A>G) in the general population?

CDK2AP2 p.Thr75Ala (c.223A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK2AP2 p.Thr75Ala (c.223A>G)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

CDK2AP2 p.Thr75Ala

c.223A>G · VCV3830858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -4.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.97, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 514 bp · p 2.4e-07 · regional, not allelic
Overall
CADD	19.78	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK2AP2
Protein: p.Thr75Ala
Coding: c.223A>G
MANE Select: NM_005851
Type: single nucleotide variant
Location: chr11:67507455 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB
Residue 75: the 'interaction with cdk2' region; an α-helix

Full CDK2AP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK2AP2 p.Gln60= Benign ★★ same type
CDK2AP2 p.Ala9Thr Uncertain significance ★ ⚠ same type
CDK2AP2 p.Glu83Gln Uncertain significance ★ ⚠ same type
CDK2AP2 p.Gly15Ser Uncertain significance ★ ⚠ same type
CDK2AP2 p.Met56Thr Uncertain significance ★ ⚠ same type
CDK2AP2 p.Met62Leu Uncertain significance ★ ⚠ same type
CDK2AP2 p.Pro19Leu Uncertain significance ★ ⚠ same type
CDK2AP2 p.Pro26Leu Uncertain significance ★ ⚠ 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/cdk2ap2-p-thr75ala (accessed [today's date]).

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