Is CDKN2A p.Val82fs (c.225_243dup) pathogenic?

CDKN2A p.Val82fs (c.225243dup) is classified Likely pathogenic in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-07). Ultra-rare (gnomAD MAF 7.186e-07); Associated with melanoma and neural system tumor syndrome.

What condition is associated with CDKN2A p.Val82fs (c.225_243dup)?

CDKN2A p.Val82fs (c.225_243dup) is associated with melanoma and neural system tumor syndrome (ClinVar).

How common is CDKN2A p.Val82fs (c.225_243dup) in the general population?

CDKN2A p.Val82fs (c.225_243dup) is ultra-rare (gnomAD MAF 7.186e-07) (gnomAD).

How is Melanoma and neural system tumor syndrome inherited?

Typically Autosomal dominant, Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

CDKN2A p.Val82fs

c.225_243dup · rs730881674 · VCV2680555

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.186e-07)

Conditions

melanoma and neural system tumor 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 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 2, phastCons 0.97

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

Population frequency

dbSNP / gnomAD

Global frequency 7.19e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: CDKN2A
Protein: p.Val82fs
Coding: c.225_243dup
MANE Select: NM_000077
dbSNP: rs730881674
Type: Duplication
Location: chr9:21971115 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 82: an α-helix; the 'disordered' region

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

Disease context

melanoma and neural system tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Melanoma and neural system tumor syndrome (Orphanet):

Inheritance: Autosomal dominant, Unknown
Onset: Adult, Elderly

Similar variants

CDKN2A p.Arg112_Leu113insArg Pathogenic ★★ same condition
CDKN2A p.Leu121fs Pathogenic/Likely pathogenic ★★ same condition
CDKN2A p.Thr137fs Uncertain significance ★★ same condition
CDKN2A p.Val82Met Uncertain significance ★★ ⚠ same residue
CDKN2A p.Leu63fs Likely pathogenic ★ same condition
CDKN2A p.Val82Glu Uncertain significance ★ ⚠ same residue
CDKN2A p.Val82Leu Uncertain significance ★ ⚠ same residue
CDKN2A p.Val82= Likely benign ★ same residue

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-val82fs (accessed [today's date]).

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