Is CDKN2A p.Gly16= (c.48C>T) pathogenic?

CDKN2A p.Gly16= (c.48C>T) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-12). Very rare (popmax 0.00224%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Gly16= (c.48C>T)?

CDKN2A p.Gly16= (c.48C>T) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Gly16= (c.48C>T) in the general population?

CDKN2A p.Gly16= (c.48C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

CDKN2A p.Gly16=

c.48C>T · rs786202556 · VCV185912

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

hereditary neoplastic syndrome

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 3.8	GERP 0.64, phastCons 1
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,648 alleles

Overall 6.89e-05% 1/1,451,630 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDKN2A
Protein: p.Gly16=
Coding: c.48C>T
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs786202556
Type: single nucleotide variant
Location: chr9:21994284 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 16: an α-helix; a UniProt-annotated variant site (in a biliary tract tumor and a familial melanoma); 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.Leu16Arg Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Leu16Pro Pathogenic/Likely pathogenic ★★ same residue
CDKN2A p.Gly16Arg Uncertain significance ★★ same residue
CDKN2A p.Gly16Asp Uncertain significance ★★ same residue
CDKN2A p.Gly16Ser Uncertain significance ★★ same residue
CDKN2A p.Leu16Gln Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gly16Val Uncertain significance ★ same residue
CDKN2A p.Leu16= 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-gly16 (accessed [today's date]).

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