Is CDKN2B p.Val84= (c.252G>C) pathogenic?

CDKN2B p.Val84= (c.252G>C) is classified Likely benign in CDKN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). Very rare (popmax 0.000254%, nfe).

How common is CDKN2B p.Val84= (c.252G>C) in the general population?

CDKN2B p.Val84= (c.252G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

CDKN2B p.Val84=

c.252G>C · rs1422575612 · VCV1802776

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 0.012	GERP 0.27, phastCons 0.81
Overall
CADD	8.474	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,874 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,758 alleles · very rare exomes 3/1,459,398 · genomes 0/152,360 · 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.Val84=
Coding: c.252G>C
MANE Select: NM_004936
dbSNP: rs1422575612
Type: single nucleotide variant
Location: chr9:22006152 (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 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
CDKN2B p.Ala50Val 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-val84 (accessed [today's date]).

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