Is CDKN2A p.Gln50Ter (c.148C>T) pathogenic?

CDKN2A p.Gln50Ter (c.148C>T) is classified Pathogenic in CDKN2A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-10-09). Absent from gnomAD v4.1; Associated with melanoma and neural system tumor syndrome.

What condition is associated with CDKN2A p.Gln50Ter (c.148C>T)?

CDKN2A p.Gln50Ter (c.148C>T) is associated with melanoma and neural system tumor syndrome, melanoma-pancreatic cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Gln50Ter (c.148C>T) in the general population?

CDKN2A p.Gln50Ter (c.148C>T) is absent from gnomAD v4.1 (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.Gln50Ter

c.148C>T · rs864622636 · VCV220711

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

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.Gln50Ter
Coding: c.148C>T
MANE Select: NM_000077
dbSNP: rs864622636
Type: single nucleotide variant
Location: chr9:21974680 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 50: an α-helix; a UniProt-annotated variant site (in cmm2); the 'interaction with cdk5rap3 and mdm2' 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

Also linked: melanoma-pancreatic cancer syndrome hereditary neoplastic syndrome familial melanoma

For Melanoma and neural system tumor syndrome (Orphanet):

Inheritance: Autosomal dominant, Unknown
Onset: Adult, Elderly

Similar variants

CDKN2A p.Gln50Arg Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Gln50Pro Likely pathogenic ★★ same residue
CDKN2A p.Gln50Leu Uncertain significance ★★ ⚠ same residue
CDKN2A p.Leu50Arg Uncertain significance ★★ same residue
CDKN2A p.Gln50= Uncertain significance ★ same residue
CDKN2A p.Gln50His Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Leu50Pro Uncertain significance ★ same residue
CDKN2A p.Gln50Lys 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-gln50ter (accessed [today's date]).

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