Is KDM6B p.Pro252= (c.756A>C) pathogenic?

KDM6B p.Pro252= (c.756A>C) is classified Likely benign in KDM6B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-04). Very rare (popmax 8.88e-05%); Associated with KDM6B-related disorder.

What condition is associated with KDM6B p.Pro252= (c.756A>C)?

KDM6B p.Pro252= (c.756A>C) is associated with KDM6B-related disorder (ClinVar).

How common is KDM6B p.Pro252= (c.756A>C) in the general population?

KDM6B p.Pro252= (c.756A>C) is very rare (popmax 8.88e-05%) (gnomAD).

KDM6B p.Pro252=

c.756A>C · rs764869334 · VCV3038016

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.88e-05%)

Conditions

KDM6B-related disorder

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 -0.064	GERP -0.62, phastCons 0.25
Overall
CADD	1.441	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.88e-05%

Overall 8.88e-05% 1/1,125,814 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: KDM6B
Protein: p.Pro252=
Coding: c.756A>C
MANE Select: NM_001348716
dbSNP: rs764869334
Type: single nucleotide variant
Location: chr17:7846863 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.54 · 6 PDB
Residue 252: the 'disordered' region; a UniProt-annotated variant site (in nedsst)

Full KDM6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KDM6B-related disorder

Similar variants

KDM6B p.Arg951Ter Pathogenic ★★ same condition
KDM6B p.Pro37Leu Uncertain significance ★★ ⚠ same condition
KDM6B p.Cys1397Tyr Likely pathogenic ★ same condition
KDM6B p.Gln858Ter Likely pathogenic ★ same condition
KDM6B p.Trp41Ter Likely pathogenic ★ same condition
KDM6B p.Ala989Val Uncertain significance ★ ⚠ same condition
KDM6B p.Arg1551Pro Uncertain significance ★ ⚠ same condition
KDM6B p.Arg1623His Uncertain significance ★ ⚠ 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/kdm6b-p-pro252 (accessed [today's date]).

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