Is CDKN2A p.Ala17Phe (c.49_50delinsTT) pathogenic?

CDKN2A p.Ala17Phe (c.4950delinsTT) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Ala17Phe (c.49_50delinsTT)?

CDKN2A p.Ala17Phe (c.49_50delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

CDKN2A p.Ala17Phe

c.49_50delinsTT · VCV4841940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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 3	GERP -1.4, phastCons 0.25
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic

Variant & gene context

Gene: CDKN2A
Protein: p.Ala17Phe
Coding: c.49_50delinsTT
MANE Select: NM_000077
Type: Indel
Location: chr9:21974778 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 17: an α-helix; the 'interaction with cdk5rap3 and mdm2' region; a UniProt-annotated variant site (in)

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.Ala17Val Uncertain significance ★★ same residue
CDKN2A p.Pro17Ser Uncertain significance ★★ same residue
CDKN2A p.Ala17= Benign/Likely benign ★★ same residue
CDKN2A p.Pro17= Benign/Likely benign ★★ same residue
CDKN2A p.Ala17Asp Uncertain significance ★ ⚠ same residue
CDKN2A p.Ala68Leu Likely pathogenic ★★ same condition
CDKN2A p.Arg128fs Likely pathogenic ★★ same condition
CDKN2A p.Asp14fs 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-ala17phe (accessed [today's date]).

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