Is CDK4 p.Val14= (c.42C>T) pathogenic?

CDK4 p.Val14= (c.42C>T) is classified Conflicting classifications of pathogenicity in CDK4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-07). Absent from gnomAD v4.1; Associated with melanoma, cutaneous malignant, susceptibility to, 3.

What condition is associated with CDK4 p.Val14= (c.42C>T)?

CDK4 p.Val14= (c.42C>T) is associated with melanoma, cutaneous malignant, susceptibility to, 3, hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDK4 p.Val14= (c.42C>T) in the general population?

CDK4 p.Val14= (c.42C>T) is absent from gnomAD v4.1 (gnomAD).

CDK4 p.Val14=

c.42C>T · rs786203182 · VCV186740

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

melanoma, cutaneous malignant, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.1
Overall
CADD	4.311	PHRED · no single calibrated threshold — expert panels disagree

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: CDK4
Protein: p.Val14=
Coding: c.42C>T
MANE Select: NM_000075
dbSNP: rs786203182
Type: single nucleotide variant
Location: chr12:57751676 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.57 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 15 PDB
Residue 14: the protein kinase domain; a binding site

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

Disease context

melanoma, cutaneous malignant, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome familial melanoma

Similar variants

CDK4 p.Val14Ala Uncertain significance ★ ⚠ same residue
CDK4 p.Val14Ile Uncertain significance ★ ⚠ same residue
CDK4 p.Val14Phe Uncertain significance ★ ⚠ same residue
CDK4 p.Arg24Cys Pathogenic ★★ same condition
CDK4 p.Arg24His Pathogenic ★★ same condition
CDK4 c.354+3G>C Uncertain significance ★★ same condition
CDK4 c.354+5G>T Uncertain significance ★★ same condition
CDK4 c.355-4C>G Uncertain significance ★★ same condition

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-val14 (accessed [today's date]).

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