CDKN2A p.Ala133fs
c.395_396dup · VCV4728613
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
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 in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 3 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP 2, phastCons 0.98 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CDKN2A
- Protein
- p.Ala133fs
- Coding
- c.395_396dup
- MANE Select
- NM_000077
- Type
- Microsatellite
- Location
- chr9:21970962 (GRCh38)
- Gene constraint
- LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.02 · 5 PDB
- Residue 133
- an α-helix
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.Ala133Ser Uncertain significance ★★ ⚠ same residue
- CDKN2A p.Ala133Thr Uncertain significance ★★ ⚠ same residue
- CDKN2A p.Ala133Val Uncertain significance ★★ ⚠ same residue
- CDKN2A p.Arg103fs Pathogenic ★★ same condition
- CDKN2A p.Leu16fs Pathogenic ★★ same condition
- CDKN2A p.Pro11_Ser12insAlaAlaGlySerSerMetGluPro Pathogenic/Likely pathogenic ★★ same condition
- CDKN2A p.Ala4_Ala5del Uncertain significance ★★ same condition
- CDKN2A c.150+7AG[4] Benign/Likely benign ★★ 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-ala133fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown