Is CDKN2A p.Ala39del (c.115_117del) pathogenic?

CDKN2A p.Ala39del (c.115117del) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-30). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Ala39del (c.115_117del)?

CDKN2A p.Ala39del (c.115_117del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Ala39del (c.115_117del) in the general population?

CDKN2A p.Ala39del (c.115_117del) is absent from gnomAD (gnomAD).

CDKN2A p.Ala39del

c.115_117del · rs2489327338 · VCV3228932

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

hereditary neoplastic syndrome

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 2.3	GERP -0.36, phastCons 0.049

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.Ala39del
Coding: c.115_117del
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs2489327338
Type: Deletion
Location: chr9:21994215 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 39: the 'interaction with cdk5rap3 and mdm2' region

Full CDKN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDKN2A p.Asn39Lys Uncertain significance ★★ ⚠ same residue
CDKN2A p.Asn39Ser Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala39= Benign/Likely benign ★★ same residue
CDKN2A p.Asn39= Likely benign ★★ same residue
CDKN2A p.Ala39Pro Uncertain significance ★ same residue
CDKN2A p.Ala39Thr 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

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-ala39del (accessed [today's date]).

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