Is CDK2 p.Asp288His (c.862G>C) pathogenic?

CDK2 p.Asp288His (c.862G>C) is classified Uncertain significance in CDK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: ambiguous (0.3481); Very rare (popmax 0.00763%, nfe).

How common is CDK2 p.Asp288His (c.862G>C) in the general population?

CDK2 p.Asp288His (c.862G>C) is very rare (popmax 0.00763%, nfe) (gnomAD).

What do computational predictors say about CDK2 p.Asp288His (c.862G>C)?

AlphaMissense predicts ambiguous (score 0.3481) — an in-silico prediction, not a clinical call.

CDK2 p.Asp288His

c.862G>C · VCV3489469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3481 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00763%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3481	ambiguous
REVEL	0.363	indeterminate
SaProt	LLR -8.67	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 2,062 bp · p 0.003 · regional, not allelic
Overall
CADD	25.7	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 0.00763% European (non-Finnish) · 90/1,180,004 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.00564% 91/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,111
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: CDK2
Protein: p.Asp288His
Coding: c.862G>C
MANE Select: NM_001798
Type: single nucleotide variant
Location: chr12:55971590 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.55 · 523 PDB
Residue 288: a turn

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.Cys191Arg Uncertain significance ★ ⚠ same type
CDK2 p.Glu57Ala Uncertain significance ★ ⚠ same type
CDK2 p.His268Leu Uncertain significance ★ ⚠ same type
CDK2 p.Ile10Leu 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-asp288his (accessed [today's date]).

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