Is CDK4 p.Arg240= (c.718C>A) pathogenic?

CDK4 p.Arg240= (c.718C>A) is classified Benign/Likely benign in CDK4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-30). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDK4 p.Arg240= (c.718C>A)?

CDK4 p.Arg240= (c.718C>A) is associated with hereditary neoplastic syndrome, melanoma, cutaneous malignant, susceptibility to, 3, familial melanoma (ClinVar).

How common is CDK4 p.Arg240= (c.718C>A) in the general population?

CDK4 p.Arg240= (c.718C>A) is absent from gnomAD v4.1 (gnomAD).

CDK4 p.Arg240=

c.718C>A · rs786203856 · VCV187602

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 3.2	GERP -0.24, phastCons 1
Overall
CADD	9.909	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.Arg240=
Coding: c.718C>A
MANE Select: NM_000075
dbSNP: rs786203856
Type: single nucleotide variant
Location: chr12:57749283 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.57 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 15 PDB
Residue 240: the protein kinase domain

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

Similar variants

CDK4 p.Arg240Gln Uncertain significance ★★ ⚠ same residue
CDK4 p.Arg240Gly Uncertain significance ★★ ⚠ same residue
CDK4 p.Arg240Pro 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-arg240 (accessed [today's date]).

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