Is CDKN2A p.Glu69Ter (c.204_205delinsTT) pathogenic?

CDKN2A p.Glu69Ter (c.204205delinsTT) is classified Pathogenic in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-17). Absent from gnomAD; Associated with familial melanoma.

What condition is associated with CDKN2A p.Glu69Ter (c.204_205delinsTT)?

CDKN2A p.Glu69Ter (c.204_205delinsTT) is associated with familial melanoma (ClinVar).

How common is CDKN2A p.Glu69Ter (c.204_205delinsTT) in the general population?

CDKN2A p.Glu69Ter (c.204_205delinsTT) is absent from gnomAD (gnomAD).

How is Familial melanoma inherited?

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

CDKN2A p.Glu69Ter

c.204_205delinsTT · rs2131095862 · VCV1075589

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Glu69Ter
Coding: c.204_205delinsTT
MANE Select: NM_000077
dbSNP: rs2131095862
Type: Indel
Location: chr9:21971154 (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

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.Glu69= Conflicting classifications of pathogenicity ★ 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.Ala68Leu Likely pathogenic ★★ same condition
CDKN2A p.Arg128fs Likely pathogenic ★★ same condition
CDKN2A p.Ala85Phe Uncertain significance ★★ 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-glu69ter (accessed [today's date]).

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