Is CDKN2A p.Ala73del (c.218_220del) pathogenic?

CDKN2A p.Ala73del (c.218220del) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). Absent from gnomAD; Associated with familial melanoma.

What condition is associated with CDKN2A p.Ala73del (c.218_220del)?

CDKN2A p.Ala73del (c.218_220del) is associated with familial melanoma (ClinVar).

How common is CDKN2A p.Ala73del (c.218_220del) in the general population?

CDKN2A p.Ala73del (c.218_220del) 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.Ala73del

c.218_220del · rs1554654136 · VCV2705674

Uncertain significance Single submitter

Classification

Uncertain significance

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
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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.Ala73del
Coding: c.218_220del
MANE Select: NM_000077
dbSNP: rs1554654136
Type: Deletion
Location: chr9:21971139 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 73: the 'disordered' 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

For Familial melanoma (Orphanet):

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

Similar variants

CDKN2A p.Ala73_Asp74insAla Uncertain significance ★★ same residue
CDKN2A p.Ala73Pro Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala73Thr Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala73= Conflicting classifications of pathogenicity ★ same residue
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

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-ala73del (accessed [today's date]).

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