Is CDKN2A p.Glu69= (c.207G>A) pathogenic?

CDKN2A p.Glu69= (c.207G>A) is classified Conflicting classifications of pathogenicity in CDKN2A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-09-16). No allele count reported in gnomAD v4.1 (AN 1,592,782); Associated with familial melanoma.

What condition is associated with CDKN2A p.Glu69= (c.207G>A)?

CDKN2A p.Glu69= (c.207G>A) is associated with familial melanoma, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Glu69= (c.207G>A) in the general population?

CDKN2A p.Glu69= (c.207G>A) is no allele count reported in gnomAD v4.1 (AN 1,592,782) (gnomAD).

How is Familial melanoma inherited?

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

CDKN2A p.Glu69=

c.207G>A · rs1587332220 · VCV663453

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,592,782)

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.084	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.85	GERP -4.1, phastCons 0.001
Overall
CADD	4.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,592,782). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKN2A
Protein: p.Glu69=
Coding: c.207G>A
MANE Select: NM_000077
dbSNP: rs1587332220
Type: single nucleotide variant
Location: chr9:21971152 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 69: a UniProt-annotated variant site (in melanoma; loss of cdk4 binding); a UniProt-annotated variant site (found in some patients with melanoma; partial loss of cdk4 binding); a UniProt-annotated variant site (in a bladder tumor); a UniProt-annotated variant site (in a lung tumor); the 'disordered' region

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

Disease context

familial melanoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Familial melanoma (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDKN2A p.Glu69Asp Uncertain significance ★★ ⚠ same residue
CDKN2A p.Glu69Ala Uncertain significance ★ ⚠ same residue
CDKN2A p.Glu69Gly Conflicting classifications of pathogenicity ★ same residue
CDKN2A p.Glu69Lys Uncertain significance ★ same residue
CDKN2A p.Glu69Ter Pathogenic ★ 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

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-glu69 (accessed [today's date]).

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