Is CDK4 p.Lys211= (c.633G>A) pathogenic?

CDK4 p.Lys211= (c.633G>A) is classified Conflicting classifications of pathogenicity in CDK4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-10). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDK4 p.Lys211= (c.633G>A)?

CDK4 p.Lys211= (c.633G>A) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDK4 p.Lys211= (c.633G>A) in the general population?

CDK4 p.Lys211= (c.633G>A) is absent from gnomAD v4.1 (gnomAD).

CDK4 p.Lys211=

c.633G>A · VCV3605196

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 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.
REVEL	0.056	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP 0.79, phastCons 1
Overall
CADD	17.06	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.Lys211=
Coding: c.633G>A
MANE Select: NM_005981 · reported on NM_000075
Type: single nucleotide variant
Location: chr12:57749504 (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: 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-lys211 (accessed [today's date]).

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