Is CDKN2A p.Gln58Arg (c.173A>G) pathogenic?

CDKN2A p.Gln58Arg (c.173A>G) is classified Uncertain significance in CDKN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-15). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Gln58Arg (c.173A>G)?

CDKN2A p.Gln58Arg (c.173A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Gln58Arg (c.173A>G) in the general population?

CDKN2A p.Gln58Arg (c.173A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

CDKN2A p.Gln58Arg

c.173A>G · rs2489326851 · VCV1779150

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.101	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP 0.24, phastCons 0.002
Overall
CADD	16.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,846 alleles

Overall 6.24e-05% 1/1,602,626 alleles · very rare exomes 1/1,450,312 · genomes 0/152,314 · 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.Gln58Arg
Coding: c.173A>G
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs2489326851
Type: single nucleotide variant
Location: chr9:21994159 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 58: an α-helix; the 'interaction with cdk5rap3 and mdm2' region; 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.Arg58Gln Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg58Gly Uncertain significance ★★ ⚠ same residue
CDKN2A p.Arg58= Benign/Likely benign ★★ same residue
CDKN2A p.Gln58Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Gln58= Likely benign ★ same residue
CDKN2A p.Arg58fs Pathogenic ★ same residue
CDKN2A p.Gln58fs Uncertain significance ★ same residue
CDKN2A p.Arg58Leu 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-gln58arg (accessed [today's date]).

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