Is CDK4 p.Gly247= (c.741A>G) pathogenic?

CDK4 p.Gly247= (c.741A>G) is classified Benign/Likely benign in CDK4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-26). Very rare (popmax 6.84e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with CDK4 p.Gly247= (c.741A>G)?

CDK4 p.Gly247= (c.741A>G) is associated with hereditary neoplastic syndrome, melanoma, cutaneous malignant, susceptibility to, 3, familial melanoma (ClinVar).

How common is CDK4 p.Gly247= (c.741A>G) in the general population?

CDK4 p.Gly247= (c.741A>G) is very rare (popmax 6.84e-05%) (gnomAD).

CDK4 p.Gly247=

c.741A>G · rs1595108773 · VCV827034

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

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 0.6	GERP -1.2, phastCons 1
Overall
CADD	11.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,780 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.Gly247=
Coding: c.741A>G
MANE Select: NM_005981 · reported on NM_000075
dbSNP: rs1595108773
Type: single nucleotide variant
Location: chr12:57749260 (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-gly247 (accessed [today's date]).

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