Is CDKN2A p.Met54del (c.154ATG[2]) pathogenic?

CDKN2A p.Met54del (c.154ATG[2]) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-08). Absent from gnomAD; Associated with familial melanoma.

What condition is associated with CDKN2A p.Met54del (c.154ATG[2])?

CDKN2A p.Met54del (c.154ATG[2]) is associated with familial melanoma, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Met54del (c.154ATG[2]) in the general population?

CDKN2A p.Met54del (c.154ATG[2]) is absent from gnomAD (gnomAD).

How is Familial melanoma inherited?

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

CDKN2A p.Met54del

c.154ATG[2] · rs2131096613 · VCV1505753

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial melanoma

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 4.8	GERP 1.2, phastCons 1

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.Met54del
Coding: c.154ATG[2]
MANE Select: NM_000077
dbSNP: rs2131096613
Type: Microsatellite
Location: chr9:21971197 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 54: the 'interaction with cdk5rap3 and mdm2' region

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

Disease context

familial melanoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Familial melanoma (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDKN2A p.Met54_Gly55insMet Uncertain significance ★ same residue
CDKN2A p.Arg54Cys Uncertain significance ★★ same residue
CDKN2A p.Arg54Ser Uncertain significance ★★ same residue
CDKN2A p.Met54Ile Uncertain significance ★★ ⚠ same residue
CDKN2A p.Met54Leu Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg54His Uncertain significance ★ same residue
CDKN2A p.Met54Arg Uncertain significance ★ ⚠ same residue
CDKN2A p.Met54Thr Uncertain significance ★ ⚠ 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-met54del (accessed [today's date]).

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