Is CDK4 p.Ter304= (c.911G>A) pathogenic?

CDK4 p.Ter304= (c.911G>A) is classified Benign in CDK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). Very rare (popmax 0.00017%, nfe); Associated with melanoma, cutaneous malignant, susceptibility to, 3.

What condition is associated with CDK4 p.Ter304= (c.911G>A)?

CDK4 p.Ter304= (c.911G>A) is associated with melanoma, cutaneous malignant, susceptibility to, 3 (ClinVar).

How common is CDK4 p.Ter304= (c.911G>A) in the general population?

CDK4 p.Ter304= (c.911G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

CDK4 p.Ter304=

c.911G>A · VCV3378665

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

melanoma, cutaneous malignant, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.55	GERP -1.5, phastCons 1
Overall
CADD	11.91	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,175,760 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,456,968 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.Ter304=
Coding: c.911G>A
MANE Select: NM_005981 · reported on NM_000075
Type: single nucleotide variant
Location: chr12:57748526 (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

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-ter304 (accessed [today's date]).

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