Is CDKN2B p.Gln52Arg (c.155A>G) pathogenic?

CDKN2B p.Gln52Arg (c.155A>G) is classified Uncertain significance in CDKN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: likely pathogenic (0.7293); Very rare (popmax 0.00034%, nfe).

How common is CDKN2B p.Gln52Arg (c.155A>G) in the general population?

CDKN2B p.Gln52Arg (c.155A>G) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about CDKN2B p.Gln52Arg (c.155A>G)?

AlphaMissense predicts likely pathogenic (score 0.7293) — an in-silico prediction, not a clinical call.

CDKN2B p.Gln52Arg

c.155A>G · rs769168016 · VCV2576500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7293	likely pathogenic
REVEL	0.501	indeterminate
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.47	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.58	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 2,963 bp · p 0.034 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,175,744 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000249% 4/1,605,368 alleles · very rare exomes 4/1,453,056 · genomes 0/152,312 · 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: CDKN2B
Protein: p.Gln52Arg
Coding: c.155A>G
MANE Select: NM_004936
dbSNP: rs769168016
Type: single nucleotide variant
Location: chr9:22008799 (GRCh38)
Gene constraint: LOEUF 1.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.12

Full CDKN2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN2B p.Gln52Pro Uncertain significance ★ ⚠ same residue
CDKN2B c.157-102G>A Benign ★★ same type
CDKN2B c.157-27C>A Benign ★★ same type
CDKN2B p.Ala120= Benign ★★ same type
CDKN2B p.Leu115= Likely benign ★★ same type
CDKN2B p.Ala129Gly Uncertain significance ★ ⚠ same type
CDKN2B p.Ala129Val Uncertain significance ★ ⚠ same type
CDKN2B p.Ala23Val Uncertain significance ★ ⚠ same type

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/cdkn2b-p-gln52arg (accessed [today's date]).

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