Is CDKN2A p.Arg3= (c.9C>A) pathogenic?

CDKN2A p.Arg3= (c.9C>A) is classified Benign/Likely benign in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-12). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Arg3= (c.9C>A)?

CDKN2A p.Arg3= (c.9C>A) is associated with hereditary neoplastic syndrome, melanoma-pancreatic cancer syndrome (ClinVar).

How common is CDKN2A p.Arg3= (c.9C>A) in the general population?

CDKN2A p.Arg3= (c.9C>A) is absent from gnomAD v4.1 (gnomAD).

CDKN2A p.Arg3=

c.9C>A · rs2489328437 · VCV1768911

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3, phastCons 0.99
Overall
CADD	11.91	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.Arg3=
Coding: c.9C>A
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs2489328437
Type: single nucleotide variant
Location: chr9:21994323 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 3: the 'interaction with cdk5rap3 and mdm2' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: melanoma-pancreatic cancer syndrome

Similar variants

CDKN2A p.Arg3Cys Uncertain significance ★★ same residue
CDKN2A p.Arg3His Uncertain significance ★★ same residue
CDKN2A p.Pro3Ala Uncertain significance ★★ ⚠ same residue
CDKN2A p.Pro3= Benign/Likely benign ★★ same residue
CDKN2A p.Arg3Leu Uncertain significance ★ same residue
CDKN2A p.Pro3Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Pro3Thr Uncertain significance ★ ⚠ same residue
CDKN2A c.150+1G>A 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-arg3 (accessed [today's date]).

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