Is CDKN2A p.Gln50Pro (c.149A>C) pathogenic?

CDKN2A p.Gln50Pro (c.149A>C) is classified Likely pathogenic in CDKN2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-11). AlphaMissense: likely pathogenic (0.7863); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Gln50Pro (c.149A>C)?

CDKN2A p.Gln50Pro (c.149A>C) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Gln50Pro (c.149A>C) in the general population?

CDKN2A p.Gln50Pro (c.149A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN2A p.Gln50Pro (c.149A>C)?

AlphaMissense predicts likely pathogenic (score 0.7863) — an in-silico prediction, not a clinical call.

CDKN2A p.Gln50Pro

c.149A>C · rs587778189 · VCV187713

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7863 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7863	likely pathogenic ✓ concordant with ClinVar
REVEL	0.752	pathogenic-leaning
SaProt	LLR -14.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Gln50Pro
Coding: c.149A>C
MANE Select: NM_000077
dbSNP: rs587778189
Type: single nucleotide variant
Location: chr9:21974679 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: melanoma-pancreatic cancer syndrome familial melanoma

Similar variants

CDKN2A p.Gln50Arg Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Gln50Ter 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-gln50pro (accessed [today's date]).

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