Is CDKN2A p.Arg107Leu (c.320_321delinsTT) pathogenic?

CDKN2A p.Arg107Leu (c.320321delinsTT) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-23). Absent from gnomAD; Associated with familial melanoma.

What condition is associated with CDKN2A p.Arg107Leu (c.320_321delinsTT)?

CDKN2A p.Arg107Leu (c.320_321delinsTT) is associated with familial melanoma, hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Arg107Leu (c.320_321delinsTT) in the general population?

CDKN2A p.Arg107Leu (c.320_321delinsTT) 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.Arg107Leu

c.320_321delinsTT · rs1819698005 · VCV1005179

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.056	GERP 0.083, phastCons 0.001
Regional constraint	o/e 1.13	unconstrained · MANE · 6,595 bp · p 0.04 · regional, not allelic

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.Arg107Leu
Coding: c.320_321delinsTT
MANE Select: NM_000077
dbSNP: rs1819698005
Type: Indel
Location: chr9:21971038 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 107: a UniProt-annotated variant site (in cmm2); a UniProt-annotated variant site (in); 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.Arg107= Uncertain significance ★★ same residue
CDKN2A p.Arg107Pro Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg107Ser Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg107Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Arg107Gly Uncertain significance ★ ⚠ same residue
CDKN2A p.Arg107His Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Ala68Leu Likely pathogenic ★★ same condition
CDKN2A p.Arg128fs Likely 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-arg107leu (accessed [today's date]).

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