Is CDK4 p.Thr102= (c.306A>G) pathogenic?

CDK4 p.Thr102= (c.306A>G) is classified Benign/Likely benign in CDK4 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Rare (popmax 0.163%, eas); Associated with familial melanoma.

What condition is associated with CDK4 p.Thr102= (c.306A>G)?

CDK4 p.Thr102= (c.306A>G) is associated with familial melanoma, melanoma, cutaneous malignant, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is CDK4 p.Thr102= (c.306A>G) in the general population?

CDK4 p.Thr102= (c.306A>G) is rare (popmax 0.163%, eas) (gnomAD).

How is Familial melanoma inherited?

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

CDK4 p.Thr102=

c.306A>G · rs201202764 · VCV184409

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, eas)

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% East Asian · 73/44,880 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.00551% 89/1,614,174 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.163%	615
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00167%	60,026
African / African-American	0.00133%	75,048
European (non-Finnish)	0.000339%	295,008

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.Thr102=
Coding: c.306A>G
MANE Select: NM_000075
dbSNP: rs201202764
Type: single nucleotide variant
Location: chr12:57751255 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.57 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 15 PDB
Residue 102: the protein kinase domain; an α-helix

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: melanoma, cutaneous malignant, susceptibility to, 3 hereditary neoplastic syndrome

For Familial melanoma (Orphanet):

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

Similar variants

CDK4 p.Thr102Ala Uncertain significance ★★ ⚠ same residue
CDK4 p.Arg24Cys Pathogenic ★★ same condition
CDK4 p.Arg24His Pathogenic ★★ same condition
CDK4 c.354+3G>C Uncertain significance ★★ same condition
CDK4 c.354+5G>T Uncertain significance ★★ same condition
CDK4 c.355-4C>G Uncertain significance ★★ same condition
CDK4 c.632+5G>A Uncertain significance ★★ same condition
CDK4 c.820-3C>T Uncertain significance ★★ same condition

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-thr102 (accessed [today's date]).

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