Is CDKN2A p.Arg4= (c.12G>A) pathogenic?

CDKN2A p.Arg4= (c.12G>A) is classified Likely benign in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-11). Absent from gnomAD v4.1; Associated with familial melanoma.

What condition is associated with CDKN2A p.Arg4= (c.12G>A)?

CDKN2A p.Arg4= (c.12G>A) is associated with familial melanoma (ClinVar).

How common is CDKN2A p.Arg4= (c.12G>A) in the general population?

CDKN2A p.Arg4= (c.12G>A) is absent from gnomAD v4.1 (gnomAD).

How is Familial melanoma inherited?

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

CDKN2A p.Arg4=

c.12G>A · rs2131149058 · VCV1650515

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial melanoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.7	GERP -2.9, phastCons 1
Overall
CADD	13.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKN2A
Protein: p.Arg4=
Coding: c.12G>A
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs2131149058
Type: single nucleotide variant
Location: chr9:21994320 (GRCh38)

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)

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-arg4 (accessed [today's date]).

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