Is CDKN2A p.Pro48= (c.144G>T) pathogenic?

CDKN2A p.Pro48= (c.144G>T) is classified Likely benign in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-27). Absent from gnomAD v4.1; Associated with familial melanoma.

What condition is associated with CDKN2A p.Pro48= (c.144G>T)?

CDKN2A p.Pro48= (c.144G>T) is associated with familial melanoma (ClinVar).

How common is CDKN2A p.Pro48= (c.144G>T) in the general population?

CDKN2A p.Pro48= (c.144G>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial melanoma inherited?

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

CDKN2A p.Pro48=

c.144G>T · rs876659638 · VCV1152133

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.98	GERP 0.14, phastCons 0.001
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN2A
Protein: p.Pro48=
Coding: c.144G>T
MANE Select: NM_000077
dbSNP: rs876659638
Type: single nucleotide variant
Location: chr9:21974684 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 48: an α-helix; a UniProt-annotated variant site (in cmm2; also found in head and neck tumor; somatic mutation); 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

For Familial melanoma (Orphanet):

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

Similar variants

CDKN2A p.Pro48Leu Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Pro48Thr Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Pro48Gln Uncertain significance ★★ ⚠ same residue
CDKN2A p.Pro48Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Met48Leu Uncertain significance ★ same residue
CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.151-1G>A Pathogenic ★★ same condition
CDKN2A c.151-1G>C 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-pro48 (accessed [today's date]).

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