Is CDK4 p.Asp99fs (c.295del) pathogenic?

CDK4 p.Asp99fs (c.295del) is classified Uncertain significance in CDK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-24). Associated with hereditary neoplastic syndrome.

What condition is associated with CDK4 p.Asp99fs (c.295del)?

CDK4 p.Asp99fs (c.295del) is associated with hereditary neoplastic syndrome (ClinVar).

CDK4 p.Asp99fs

c.295del · VCV4868604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CDK4
Protein: p.Asp99fs
Coding: c.295del
MANE Select: NM_000075
Type: Deletion
Location: chr12:57751266 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.57 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 15 PDB
Residue 99: the protein kinase domain; a β-strand

Full CDK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK4 p.Asp99= Likely benign ★★ same residue
CDK4 p.Ala58_Arg62del Uncertain significance ★★ same condition
CDK4 p.Glu184fs Uncertain significance ★★ same condition
CDK4 p.Phe159fs Uncertain significance ★★ same condition
CDK4 p.Ala289fs Uncertain significance ★ same condition
CDK4 p.Arg252fs Uncertain significance ★ same condition
CDK4 p.Asp99Asn Uncertain significance ★ ⚠ same residue
CDK4 p.Asp99Glu Uncertain significance ★ ⚠ same residue

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/cdk4-p-asp99fs (accessed [today's date]).

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