KDM6B p.Pro196=
c.588G>A · rs143632454 · VCV754856
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, afr)
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 -2.8 | GERP -3.1 |
| Overall | ||
| CADD | 1.316 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
African / African-American · 18/74,886 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.00328%
53/1,613,936 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.024% | 4,160 |
| East Asian | 0.00668% | 14,961 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| South Asian | 0.00439% | 22,770 |
| Admixed American | 0.00333% | 29,999 |
| European (non-Finnish) | 0.00195% | 51,304 |
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.Pro196=
- Coding
- c.588G>A
- MANE Select
- NM_001348716
- dbSNP
- rs143632454
- Type
- single nucleotide variant
- Location
- chr17:7846617 (GRCh38)
- Gene constraint
- LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.54 · 6 PDB
- Residue 196
- the 'disordered' region; a UniProt-annotated variant site (in nedsst)
Similar variants
- KDM6B p.Pro196Ala Uncertain significance ★ ⚠ same residue
- KDM6B p.Pro196Leu Uncertain significance ★ ⚠ same residue
- KDM6B p.Arg1499Ter Pathogenic/Likely pathogenic ★★ same type
- KDM6B p.Arg166Ter Pathogenic ★★ same type
- KDM6B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same type
- KDM6B p.Arg229Ter Pathogenic/Likely pathogenic ★★ same type
- KDM6B p.Arg495Ter Pathogenic/Likely pathogenic ★★ same type
- KDM6B p.Arg951Ter Pathogenic ★★ 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/kdm6b-p-pro196 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown