Is CDK4 p.Arg288= (c.864A>T) pathogenic?

CDK4 p.Arg288= (c.864A>T) is classified Conflicting classifications of pathogenicity in CDK4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-19). Very rare (popmax 0.00401%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with CDK4 p.Arg288= (c.864A>T)?

CDK4 p.Arg288= (c.864A>T) is associated with hereditary neoplastic syndrome, melanoma, cutaneous malignant, susceptibility to, 3, familial melanoma (ClinVar).

How common is CDK4 p.Arg288= (c.864A>T) in the general population?

CDK4 p.Arg288= (c.864A>T) is very rare (popmax 0.00401%, afr) (gnomAD).

CDK4 p.Arg288=

c.864A>T · rs1369349270 · VCV1089164

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.14	GERP 1.1, phastCons 0.99
Overall
CADD	18.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,906 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,890 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: CDK4
Protein: p.Arg288=
Coding: c.864A>T
MANE Select: NM_005981 · reported on NM_000075
dbSNP: rs1369349270
Type: single nucleotide variant
Location: chr12:57748573 (GRCh38)

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

Also linked: melanoma, cutaneous malignant, susceptibility to, 3 familial melanoma

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-arg288 (accessed [today's date]).

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