Is CDKN2A p.Arg107= (c.321C>T) pathogenic?

CDKN2A p.Arg107= (c.321C>T) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-12). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Arg107= (c.321C>T)?

CDKN2A p.Arg107= (c.321C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Arg107= (c.321C>T) in the general population?

CDKN2A p.Arg107= (c.321C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CDKN2A p.Arg107=

c.321C>T · rs772527888 · VCV1729052

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 -0.056	GERP 0.083, phastCons 0.001
Overall
CADD	8.526	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,380 alleles

Overall 6.88e-05% 1/1,453,704 alleles · very rare

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.Arg107=
Coding: c.321C>T
MANE Select: NM_000077
dbSNP: rs772527888
Type: single nucleotide variant
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

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

Similar variants

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.Arg107Leu Uncertain significance ★★ same residue
CDKN2A c.150+2T>G Likely pathogenic ★★ same condition
CDKN2A c.151-1G>C 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-arg107 (accessed [today's date]).

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