Is CDKN2A p.Gln57= (c.171G>A) pathogenic?

CDKN2A p.Gln57= (c.171G>A) is classified Likely benign in CDKN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-07). Very rare (popmax 0.00892%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDKN2A p.Gln57= (c.171G>A)?

CDKN2A p.Gln57= (c.171G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDKN2A p.Gln57= (c.171G>A) in the general population?

CDKN2A p.Gln57= (c.171G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

CDKN2A p.Gln57=

c.171G>A · rs1391696399 · VCV1778715

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

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 0.36	GERP 0.54, phastCons 0.99
Overall
CADD	11.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,858 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00025% 4/1,602,622 alleles · very rare exomes 4/1,450,296 · genomes 0/152,326 · 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.Gln57=
Coding: c.171G>A
MANE Select: NM_000077 · reported on NM_058195
dbSNP: rs1391696399
Type: single nucleotide variant
Location: chr9:21994161 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.02 · 5 PDB
Residue 57: an α-helix; a UniProt-annotated variant site (in pancreas carcinoma; somatic mutation; partial loss of cdk4 binding); 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.Ala57Asp Uncertain significance ★★ same residue
CDKN2A p.Ala57Gly Uncertain significance ★★ ⚠ same residue
CDKN2A p.Gln57Arg Uncertain significance ★★ same residue
CDKN2A p.Ala57Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CDKN2A p.Gln57His Uncertain significance ★ same residue
CDKN2A p.Ala57= Likely benign ★ same residue
CDKN2A p.Ala57Thr Likely benign ★ same residue
CDKN2A p.Gln57Ter Pathogenic ★ 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-gln57 (accessed [today's date]).

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