Is CDK4 p.Ala248= (c.744C>T) pathogenic?

CDK4 p.Ala248= (c.744C>T) is classified Benign/Likely benign in CDK4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-26). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDK4 p.Ala248= (c.744C>T)?

CDK4 p.Ala248= (c.744C>T) is associated with hereditary neoplastic syndrome, melanoma, cutaneous malignant, susceptibility to, 3, familial melanoma (ClinVar).

How common is CDK4 p.Ala248= (c.744C>T) in the general population?

CDK4 p.Ala248= (c.744C>T) is absent from gnomAD v4.1 (gnomAD).

CDK4 p.Ala248=

c.744C>T · rs1595108768 · VCV1127442

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 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 looked up on this page · why
Constraint at this position
Conservation	phyloP 6.4	GERP 0.95, phastCons 1
Overall
CADD	12.1	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.Ala248=
Coding: c.744C>T
MANE Select: NM_005981 · reported on NM_000075
dbSNP: rs1595108768
Type: single nucleotide variant
Location: chr12:57749257 (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-ala248 (accessed [today's date]).

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