Is CDK4 p.Thr116Arg (c.347_348delinsGA) pathogenic?

CDK4 p.Thr116Arg (c.347348delinsGA) is classified Uncertain significance in CDK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). Absent from gnomAD; Associated with familial melanoma.

What condition is associated with CDK4 p.Thr116Arg (c.347_348delinsGA)?

CDK4 p.Thr116Arg (c.347_348delinsGA) is associated with familial melanoma (ClinVar).

How common is CDK4 p.Thr116Arg (c.347_348delinsGA) in the general population?

CDK4 p.Thr116Arg (c.347_348delinsGA) is absent from gnomAD (gnomAD).

How is Familial melanoma inherited?

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

CDK4 p.Thr116Arg

c.347_348delinsGA · rs2540902217 · VCV2862183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP -1.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 3,189 bp · p 2e-07 · regional, not allelic

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.Thr116Arg
Coding: c.347_348delinsGA
MANE Select: NM_000075
dbSNP: rs2540902217
Type: Indel
Location: chr12:57751213 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.57 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 15 PDB
Residue 116: 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

For Familial melanoma (Orphanet):

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

Similar variants

CDK4 p.Thr116Met Uncertain significance ★★ ⚠ same residue
CDK4 p.Thr116= Benign/Likely benign ★★ same residue
CDK4 p.Thr116Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CDK4 c.218+6_218+7delinsGT Uncertain significance ★ same condition
CDK4 p.Arg163Ala Uncertain significance ★ same condition
CDK4 p.Pro250Tyr Uncertain significance ★ same condition
CDK4 p.Arg24Cys Pathogenic ★★ same condition
CDK4 p.Arg24His Pathogenic ★★ ⚠ 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-thr116arg (accessed [today's date]).

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