Is CDK2 p.Lys105Glu (c.313A>G) pathogenic?

CDK2 p.Lys105Glu (c.313A>G) is classified Uncertain significance in CDK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely pathogenic (0.9447); Very rare (popmax 8.47e-05%, nfe).

How common is CDK2 p.Lys105Glu (c.313A>G) in the general population?

CDK2 p.Lys105Glu (c.313A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CDK2 p.Lys105Glu (c.313A>G)?

AlphaMissense predicts likely pathogenic (score 0.9447) — an in-silico prediction, not a clinical call.

CDK2 p.Lys105Glu

c.313A>G · VCV3265445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9447 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9447	likely pathogenic
REVEL	0.513	indeterminate
SaProt	LLR -14.91	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 756 bp · p 0.1 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,948 alleles

Overall 6.84e-05% 1/1,461,836 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: CDK2
Protein: p.Lys105Glu
Coding: c.313A>G
MANE Select: NM_001798
Type: single nucleotide variant
Location: chr12:55968167 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.55 · 523 PDB
Residue 105: the protein kinase domain; an α-helix

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-lys105glu (accessed [today's date]).

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