Is CDKN2A p.Phe5del (c.15_17del) pathogenic?

CDKN2A p.Phe5del (c.1517del) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-27). Absent from gnomAD; Associated with familial melanoma.

What condition is associated with CDKN2A p.Phe5del (c.15_17del)?

CDKN2A p.Phe5del (c.15_17del) is associated with familial melanoma, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Phe5del (c.15_17del) in the general population?

CDKN2A p.Phe5del (c.15_17del) 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.

CDKN2A p.Phe5del

c.15_17del · rs1587358674 · VCV660178

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 0.56	GERP 1.5, phastCons 0.97

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: CDKN2A
Protein: p.Phe5del
Coding: c.15_17del
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs1587358674
Type: Deletion
Location: chr9:21994315 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 5: a β-strand; the 'interaction with cdk5rap3 and mdm2' region

Full CDKN2A 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: hereditary neoplastic syndrome

For Familial melanoma (Orphanet):

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

Similar variants

CDKN2A p.Ala5Glu Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala5Thr Uncertain significance ★★ same residue
CDKN2A p.Ala5Val Uncertain significance ★★ ⚠ same residue
CDKN2A p.Phe5Ile Uncertain significance ★★ same residue
CDKN2A p.Phe5Leu Uncertain significance ★★ same residue
CDKN2A p.Phe5Tyr Uncertain significance ★★ same residue
CDKN2A p.Ala5= Benign/Likely benign ★★ same residue
CDKN2A p.Phe5= Benign/Likely benign ★★ same residue

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-phe5del (accessed [today's date]).

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