CDKN2A p.Ala36Pro
c.106G>C · rs1587358428 · VCV647557
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
familial melanoma
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.119 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.37 | GERP -1.7 |
| Overall | ||
| CADD | 21.9 | PHRED · no single calibrated threshold — expert panels disagree |
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
- CDKN2A
- Protein
- p.Ala36Pro
- Coding
- c.106G>C
- MANE Select
- NM_000077 · reported on NM_058195
- dbSNP
- rs1587358428
- Type
- single nucleotide variant
- Location
- chr9:21994226 (GRCh38)
- Gene constraint
- LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.02 · 5 PDB
- Residue 36
- the 'interaction with cdk5rap3 and mdm2' region
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
- CDKN2A p.Ala36Ser Uncertain significance ★★ ⚠ same residue
- CDKN2A p.Ala36Thr Uncertain significance ★★ ⚠ same residue
- CDKN2A p.Ala36Val Uncertain significance ★★ ⚠ same residue
- CDKN2A p.Ala36= Benign/Likely benign ★★ same residue
- CDKN2A p.Ala36Glu Uncertain significance ★ same residue
- CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
- CDKN2A c.151-1G>A Pathogenic ★★ same condition
- CDKN2A c.151-1G>C 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/cdkn2a-p-ala36pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown