Is CDK4 p.Asp236fs (c.694_706dup) pathogenic?

CDK4 p.Asp236fs (c.694706dup) is classified Uncertain significance in CDK4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-03). No gnomAD frequency available for this variant; Associated with familial melanoma.

What condition is associated with CDK4 p.Asp236fs (c.694_706dup)?

CDK4 p.Asp236fs (c.694_706dup) is associated with familial melanoma, hereditary neoplastic syndrome (ClinVar).

How common is CDK4 p.Asp236fs (c.694_706dup) in the general population?

CDK4 p.Asp236fs (c.694_706dup) is no gnomAD frequency available for this variant (gnomAD).

How is Familial melanoma inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

CDK4 p.Asp236fs

c.694_706dup · rs2540896304 · VCV2603199

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDK4
Protein: p.Asp236fs
Coding: c.694_706dup
MANE Select: NM_005981 · reported on NM_000075
dbSNP: rs2540896304
Type: Duplication
Location: chr12:57749294 (GRCh38)

Full CDK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial melanoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Familial melanoma (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

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-asp236fs (accessed [today's date]).

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