Is CDKN1B p.Phe33fs (c.99del) pathogenic?

CDKN1B p.Phe33fs (c.99del) is classified Pathogenic/Likely pathogenic in CDKN1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-19). Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN1B p.Phe33fs (c.99del)?

CDKN1B p.Phe33fs (c.99del) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 4 (ClinVar).

CDKN1B p.Phe33fs

c.99del · VCV3999746

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1

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

Variant & gene context

Gene: CDKN1B
Protein: p.Phe33fs
Coding: c.99del
MANE Select: NM_004064
Type: Deletion
Location: chr12:12717938 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI 0.24 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.08 · 19 PDB
Residue 33: the 'disordered' region

Full CDKN1B 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

Also linked: multiple endocrine neoplasia type 4

Similar variants

CDKN1B p.Phe33Leu Uncertain significance ★★ ⚠ same residue
CDKN1B p.Phe33= Conflicting classifications of pathogenicity ★ same residue
CDKN1B p.Cys99fs Pathogenic ★★ same condition
CDKN1B p.Gln107fs Pathogenic ★★ same condition
CDKN1B p.Gly97fs Pathogenic ★★ same condition
CDKN1B p.Leu130fs Pathogenic ★★ same condition
CDKN1B p.Pro137fs Pathogenic ★★ same condition
CDKN1B p.Val109fs 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/cdkn1b-p-phe33fs (accessed [today's date]).

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