Is CDKN2A p.Gln50His (c.150G>C) pathogenic?

CDKN2A p.Gln50His (c.150G>C) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-25). AlphaMissense: likely pathogenic (0.7198); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Gln50His (c.150G>C)?

CDKN2A p.Gln50His (c.150G>C) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Gln50His (c.150G>C) in the general population?

CDKN2A p.Gln50His (c.150G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKN2A p.Gln50His (c.150G>C)?

AlphaMissense predicts likely pathogenic (score 0.7198) — an in-silico prediction, not a clinical call.

CDKN2A p.Gln50His

c.150G>C · rs1057519882 · VCV1045852

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7198 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7198	likely pathogenic
REVEL	0.508	indeterminate
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.31	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.70	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.6	GERP 2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	24.8	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.Gln50His
Coding: c.150G>C
MANE Select: NM_000077
dbSNP: rs1057519882
Type: single nucleotide variant
Location: chr9:21974678 (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: familial melanoma

Similar variants

CDKN2A p.Gln50Arg Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Gln50Pro 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.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-gln50his (accessed [today's date]).

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