Is CDKN2A p.Leu55fs (c.160_161dup) pathogenic?

CDKN2A p.Leu55fs (c.160161dup) is classified Uncertain significance in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-18). Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Leu55fs (c.160_161dup)?

CDKN2A p.Leu55fs (c.160_161dup) is associated with hereditary neoplastic syndrome (ClinVar).

CDKN2A p.Leu55fs

c.160_161dup · VCV3830979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -2.8, phastCons 0.009

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CDKN2A
Protein: p.Leu55fs
Coding: c.160_161dup
MANE Select: NM_000077 · reported on NM_058195
Type: Duplication
Location: chr9:21994170 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 55: 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.Leu55= Benign/Likely benign ★★ same residue
CDKN2A p.Gly55Ala Uncertain significance ★ ⚠ same residue
CDKN2A p.Leu55Val Conflicting classifications of pathogenicity ★ same residue
CDKN2A p.Arg112_Leu113insArg Pathogenic ★★ same condition
CDKN2A p.Arg46fs Pathogenic ★★ same condition
CDKN2A p.Ser43Ter Pathogenic ★★ same condition
CDKN2A p.Ser8fs Pathogenic ★★ same condition
CDKN2A p.Ala73_Asp74insAla Uncertain significance ★★ 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-leu55fs (accessed [today's date]).

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