Is KDM6B p.Ala884= (c.2652G>T) pathogenic?

KDM6B p.Ala884= (c.2652G>T) is classified Likely benign in KDM6B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-06-15). Very rare (popmax 0.00134%, afr); Associated with KDM6B-related disorder.

What condition is associated with KDM6B p.Ala884= (c.2652G>T)?

KDM6B p.Ala884= (c.2652G>T) is associated with KDM6B-related disorder (ClinVar).

How common is KDM6B p.Ala884= (c.2652G>T) in the general population?

KDM6B p.Ala884= (c.2652G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

KDM6B p.Ala884=

c.2652G>T · rs779781827 · VCV3029128

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 -3	GERP -3
Overall
CADD	0.149	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,418 alleles

Filtering AF 0.00062% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000477%

Overall 0.00118% 17/1,444,464 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00325%	30,768
Finnishnot grpmax-eligible	0.00165%	60,436
African / African-Americangrpmax	0.00134%	74,418
European (non-Finnish)	0.00111%	90,055

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala884=
Coding: c.2652G>T
MANE Select: NM_001348716
dbSNP: rs779781827
Type: single nucleotide variant
Location: chr17:7848940 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.54 · 6 PDB
Residue 884: a UniProt-annotated variant site (in nedsst); the 'disordered' region

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

Disease context

KDM6B-related disorder

Similar variants

KDM6B p.Ala884Gly Uncertain significance ★★ ⚠ same residue
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

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-ala884 (accessed [today's date]).

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