Is CDK2 p.Ile10Leu (c.28A>C) pathogenic?

CDK2 p.Ile10Leu (c.28A>C) is classified Uncertain significance in CDK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely pathogenic (0.5919); Absent from gnomAD v4.1.

How common is CDK2 p.Ile10Leu (c.28A>C) in the general population?

CDK2 p.Ile10Leu (c.28A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK2 p.Ile10Leu (c.28A>C)?

AlphaMissense predicts likely pathogenic (score 0.5919) — an in-silico prediction, not a clinical call.

CDK2 p.Ile10Leu

c.28A>C · rs1336824730 · VCV3141536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5919 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5919	likely pathogenic
REVEL	0.273	benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 1,122 bp · p 7e-12 · regional, not allelic
Overall
CADD	28.6	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

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: CDK2
Protein: p.Ile10Leu
Coding: c.28A>C
MANE Select: NM_001798
dbSNP: rs1336824730
Type: single nucleotide variant
Location: chr12:55967036 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.55 · 523 PDB
Residue 10: the protein kinase domain; a binding site; a β-strand

Full CDK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK2 p.Arg199His Uncertain significance ★ ⚠ same type
CDK2 p.Arg200Gln Uncertain significance ★ ⚠ same type
CDK2 p.Arg200Trp Uncertain significance ★ ⚠ same type
CDK2 p.Arg214Gln Uncertain significance ★ ⚠ same type
CDK2 p.Asp288His Uncertain significance ★ ⚠ same type
CDK2 p.Cys191Arg Uncertain significance ★ ⚠ same type
CDK2 p.Glu57Ala Uncertain significance ★ ⚠ same type
CDK2 p.His268Leu 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/cdk2-p-ile10leu (accessed [today's date]).

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