Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5358 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
familial melanoma
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5358 | ambiguous |
|---|---|---|
| REVEL | 0.336 | indeterminate |
| SaProt | LLR -11.97 | damaging |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 0.96, phastCons 1 |
| Regional constraint | o/e 0.74 | unconstrained · MANE · 3,189 bp · p 2e-07 · regional, not allelic |
| Overall | ||
| CADD | 28.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CDK4
- Protein
- p.Arg82Pro
- Coding
- c.245G>C
- MANE Select
- NM_000075
- dbSNP
- rs3211612
- Type
- single nucleotide variant
- Location
- chr12:57751316 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI 0.57 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 15 PDB
- Residue 82
- a UniProt-annotated variant site (in); the protein kinase domain; a β-strand
Disease context
familial melanoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Familial melanoma (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial
- Onset
- Adult
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- CDK4 p.Arg82Gln Uncertain significance ★★ ⚠ same residue
- CDK4 p.Arg82Gly Uncertain significance ★★ ⚠ same residue
- CDK4 p.Arg82= Benign/Likely benign ★★ same residue
- CDK4 p.Arg82Leu Uncertain significance ★ ⚠ same residue
- CDK4 p.Arg82Ter 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
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-arg82pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown