Is CDKN2A p.Arg13Cys (c.37C>T) pathogenic?

CDKN2A p.Arg13Cys (c.37C>T) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-19). Very rare (popmax 8.5e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Arg13Cys (c.37C>T)?

CDKN2A p.Arg13Cys (c.37C>T) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDKN2A p.Arg13Cys (c.37C>T) in the general population?

CDKN2A p.Arg13Cys (c.37C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

CDKN2A p.Arg13Cys

c.37C>T · rs1389587108 · VCV1023233

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.455	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.64, phastCons 1
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,175,986 alleles

Overall 6.23e-05% 1/1,604,146 alleles · very rare exomes 1/1,451,918 · genomes 0/152,228 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDKN2A
Protein: p.Arg13Cys
Coding: c.37C>T
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs1389587108
Type: single nucleotide variant
Location: chr9:21994295 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 13: an α-helix; 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: familial melanoma

Similar variants

CDKN2A p.Ala13Asp Uncertain significance ★★ same residue
CDKN2A p.Ala13Ser Uncertain significance ★★ ⚠ same residue
CDKN2A p.Ala13Val Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg13= Benign/Likely benign ★★ same residue
CDKN2A p.Arg13Ser Uncertain significance ★ same residue
CDKN2A p.Ala13= Likely benign ★ same residue
CDKN2A p.Ala13fs Pathogenic ★ same residue
CDKN2A p.Arg13His Uncertain significance ★ same residue

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-arg13cys (accessed [today's date]).

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