Is CDKN2A p.Glu88Gln (c.262G>C) pathogenic?

CDKN2A p.Glu88Gln (c.262G>C) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-05-14). AlphaMissense: ambiguous (0.3834); Very rare (popmax 8.48e-05%, nfe); Associated with melanoma-pancreatic cancer syndrome.

What condition is associated with CDKN2A p.Glu88Gln (c.262G>C)?

CDKN2A p.Glu88Gln (c.262G>C) is associated with melanoma-pancreatic cancer syndrome, melanoma, cutaneous malignant, susceptibility to, 2, melanoma and neural system tumor syndrome (ClinVar).

How common is CDKN2A p.Glu88Gln (c.262G>C) in the general population?

CDKN2A p.Glu88Gln (c.262G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDKN2A p.Glu88Gln (c.262G>C)?

AlphaMissense predicts ambiguous (score 0.3834) — an in-silico prediction, not a clinical call.

CDKN2A p.Glu88Gln

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.262G>C · rs121913384 · VCV619828

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

melanoma-pancreatic cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.3834	ambiguous
REVEL	0.457	indeterminate
SaProt	LLR -9.84	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,574 alleles

Overall 6.88e-05% 1/1,452,574 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.Glu88Gln
Coding: c.262G>C
MANE Select: NM_000077
dbSNP: rs121913384
Type: single nucleotide variant
Location: chr9:21971097 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 88: a UniProt-annotated variant site (in a biliary tract tumor); 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

Also linked: melanoma, cutaneous malignant, susceptibility to, 2 melanoma and neural system tumor syndrome hereditary neoplastic syndrome familial melanoma

For Familial atypical multiple mole melanoma syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

CDKN2A p.Glu88Ter Pathogenic ★★ same residue
CDKN2A p.Glu88Lys Uncertain significance ★★ ⚠ same residue
CDKN2A p.Glu88= Likely benign ★★ same residue
CDKN2A p.Glu88Val Uncertain significance ★ ⚠ same residue
CDKN2A c.150+1G>A Likely pathogenic ★★ same condition
CDKN2A c.150+2T>G Likely pathogenic ★★ same condition
CDKN2A c.151-1G>A Pathogenic ★★ same condition
CDKN2A c.151-1G>C Pathogenic ★★ same condition

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-glu88gln (accessed [today's date]).

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