Is CDK4 p.Asn217= (c.651C>T) pathogenic?

CDK4 p.Asn217= (c.651C>T) is classified Benign/Likely benign in CDK4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-19). Absent from gnomAD v4.1; Associated with melanoma, cutaneous malignant, susceptibility to, 3.

What condition is associated with CDK4 p.Asn217= (c.651C>T)?

CDK4 p.Asn217= (c.651C>T) is associated with melanoma, cutaneous malignant, susceptibility to, 3, hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDK4 p.Asn217= (c.651C>T) in the general population?

CDK4 p.Asn217= (c.651C>T) is absent from gnomAD v4.1 (gnomAD).

CDK4 p.Asn217=

c.651C>T · rs876659462 · VCV231956

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 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.
REVEL	0.124	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.7	GERP -0.19, phastCons 1
Overall
CADD	8.59	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.Asn217=
Coding: c.651C>T
MANE Select: NM_005981 · reported on NM_000075
dbSNP: rs876659462
Type: single nucleotide variant
Location: chr12:57749486 (GRCh38)

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

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-asn217 (accessed [today's date]).

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