Is CDKN2A c.457+17del pathogenic?

CDKN2A c.457+17del is classified Likely benign in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-19). Absent from gnomAD; Associated with familial melanoma.

What condition is associated with CDKN2A c.457+17del?

CDKN2A c.457+17del is associated with familial melanoma (ClinVar).

How common is CDKN2A c.457+17del in the general population?

CDKN2A c.457+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 c.457+17del

rs2489272654 · VCV2865752

Likely benign Single submitter

Classification

Likely benign

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
Splice region	donor +17	near-intronic (+17 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.14	GERP -0.77
Non-coding constraint	Z 3.99	1 kb window · o/e 0.76 · regional · uncalibrated

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
Coding: c.457+17del
MANE Select: NM_000077
dbSNP: rs2489272654
Type: Deletion
Location: chr9:21970885 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB

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

For Familial melanoma (Orphanet):

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

Similar variants

CDKN2A c.193+1del Likely pathogenic ★★ same condition
CDKN2A c.457+1_457+10del Pathogenic/Likely pathogenic ★★ same condition
CDKN2A p.Ala76fs Pathogenic/Likely pathogenic ★★ same condition
CDKN2A p.Glu120fs Pathogenic ★★ same condition
CDKN2A p.His123fs Pathogenic ★★ same condition
CDKN2A p.Leu32_Leu37del Pathogenic ★★ same condition
CDKN2A p.Leu64fs Pathogenic ★★ same condition
CDKN2A p.Pro114fs Pathogenic/Likely 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-c-457-plus-17del (accessed [today's date]).

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