Is CDKN2A p.Gln57Ter (c.169C>T) pathogenic?

CDKN2A p.Gln57Ter (c.169C>T) is classified Pathogenic in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). Absent from gnomAD v4.1; Associated with melanoma-pancreatic cancer syndrome.

What condition is associated with CDKN2A p.Gln57Ter (c.169C>T)?

CDKN2A p.Gln57Ter (c.169C>T) is associated with melanoma-pancreatic cancer syndrome (ClinVar).

How common is CDKN2A p.Gln57Ter (c.169C>T) in the general population?

CDKN2A p.Gln57Ter (c.169C>T) is absent from gnomAD v4.1 (gnomAD).

CDKN2A p.Gln57Ter

Q: How is Familial atypical multiple mole melanoma syndrome inherited?

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

c.169C>T · VCV4294165

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

melanoma-pancreatic cancer 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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.2, phastCons 1
Overall
CADD	37.0	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.Gln57Ter
Coding: c.169C>T
MANE Select: NM_000077 · reported on NM_058195
Type: single nucleotide variant
Location: chr9:21994163 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 57: an α-helix; a UniProt-annotated variant site (in pancreas carcinoma; somatic mutation; partial loss of cdk4 binding); the 'interaction with cdk5rap3 and mdm2' region; the 'disordered' region

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

Disease context

melanoma-pancreatic cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial atypical multiple mole melanoma syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

CDKN2A p.Ala57Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Ala57Asp Uncertain significance ★★ same residue
CDKN2A p.Ala57Gly Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gln57Arg Uncertain significance ★★ same residue
CDKN2A p.Gln57His Uncertain significance ★ same residue
CDKN2A p.Ala57= Likely benign ★ same residue
CDKN2A p.Ala57Thr Likely benign ★ same residue
CDKN2A p.Gln57= 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-gln57ter (accessed [today's date]).

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