Is CDKN2A p.Asp84= (c.252C>T) pathogenic?

CDKN2A p.Asp84= (c.252C>T) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). Very rare (popmax 0.00133%, afr); Associated with familial melanoma.

What condition is associated with CDKN2A p.Asp84= (c.252C>T)?

CDKN2A p.Asp84= (c.252C>T) is associated with familial melanoma, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Asp84= (c.252C>T) in the general population?

CDKN2A p.Asp84= (c.252C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Familial melanoma inherited?

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

CDKN2A p.Asp84=

c.252C>T · rs1472715728 · VCV845901

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.619	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.2, phastCons 1
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,022 alleles

Overall 0.000138% 2/1,452,156 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,022
European (non-Finnish)	8.48e-05%	1,179,569

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDKN2A
Protein: p.Asp84=
Coding: c.252C>T
MANE Select: NM_000077
dbSNP: rs1472715728
Type: single nucleotide variant
Location: chr9:21971107 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 84: an α-helix; a UniProt-annotated variant site (in a bladder tumor); a UniProt-annotated variant site (in non-small cell lung carcinoma); a UniProt-annotated variant site (in an esophagus tumor; also found in head and neck tumor; also found in a lung tumor); a UniProt-annotated variant site (in cmm2; also found in a lung tumor and a prostate tumor); the 'disordered' 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.Asp84Ala Pathogenic/Likely pathogenic ★★ ⚠ same residue
CDKN2A p.Asp84Asn Likely pathogenic ★★ same residue
CDKN2A p.Asp84Val Likely pathogenic ★ same residue
CDKN2A p.Asp84Glu Uncertain significance ★ ⚠ same residue
CDKN2A p.Asp84His Uncertain significance ★ ⚠ same residue
CDKN2A p.Asp84Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.150+2T>G Likely 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-asp84 (accessed [today's date]).

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