Is CDKN2A p.Thr18fs (c.47_51dup) pathogenic?

CDKN2A p.Thr18fs (c.4751dup) is classified Pathogenic in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Thr18fs (c.47_51dup)?

CDKN2A p.Thr18fs (c.47_51dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Thr18fs (c.47_51dup) in the general population?

CDKN2A p.Thr18fs (c.47_51dup) is absent from gnomAD (gnomAD).

CDKN2A p.Thr18fs

c.47_51dup · rs2489292008 · VCV3230260

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
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 -6.1	GERP -4.1

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

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.Thr18fs
Coding: c.47_51dup
MANE Select: NM_000077
dbSNP: rs2489292008
Type: Duplication
Location: chr9:21974776 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 18: an α-helix; 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.Pro18Arg Uncertain significance ★★ same residue
CDKN2A p.Pro18Leu Uncertain significance ★★ same residue
CDKN2A p.Thr18Lys Uncertain significance ★★ ⚠ same residue
CDKN2A p.Pro18= Benign/Likely benign ★★ same residue
CDKN2A p.Thr18Pro Likely pathogenic ★ ⚠ same residue
CDKN2A p.Thr18Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Arg112_Leu113insArg Pathogenic ★★ same condition
CDKN2A p.Arg46fs 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-thr18fs (accessed [today's date]).

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