KDM6B p.Pro356=
c.1068C>T · VCV4681566
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.81 | GERP 0.076, phastCons 0.005 |
| Overall | ||
| CADD | 11.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,076 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.00131%
21/1,604,082 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,215 |
| African / African-American | 0.004% | 24,973 |
| East Asian | 0.00223% | 44,850 |
| Admixed American | 0.00167% | 59,988 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,432 |
| European (non-Finnish) | 0.000848% | 117,977 |
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.Pro356=
- Coding
- c.1068C>T
- MANE Select
- NM_001348716
- Type
- single nucleotide variant
- Location
- chr17:7847263 (GRCh38)
- Gene constraint
- LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.54 · 6 PDB
- Residue 356
- the 'disordered' region; a UniProt-annotated variant site (in nedsst)
Similar variants
- KDM6B p.Pro356His 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
- KDM6B p.Ala1219Val 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/kdm6b-p-pro356 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown