UNC45B p.Leu596=
c.1788C>T · rs8075756 · VCV1260761
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 15%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -3.7 |
| Overall | ||
| CADD | 4.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
15%
African / African-American · 11,287/75,000 alleles
Filtering AF
14.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 14.7%
Overall
3.41%
55,059/1,614,072 alleles · common
exomes 45,922/1,461,816 · genomes 9,137/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 15% | 7 |
| South Asian | 9.39% | 11 |
| Amishnot grpmax-eligible | 8.02% | 12 |
| Middle Eastern | 4.17% | 24 |
| Ashkenazi Jewishnot grpmax-eligible | 4.11% | 24 |
| Remaining individualsnot grpmax-eligible | 3.82% | 26 |
| East Asian | 2.77% | 36 |
| European (non-Finnish) | 2.38% | 42 |
| Admixed American | 1.89% | 53 |
| Finnishnot grpmax-eligible | 1.27% | 79 |
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
- UNC45B
- Protein
- p.Leu596=
- Coding
- c.1788C>T
- MANE Select
- NM_001267052
- dbSNP
- rs8075756
- Type
- single nucleotide variant
- Location
- chr17:35171420 (GRCh38)
- Gene constraint
- LOEUF 0.969 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.38
Similar variants
- UNC45B p.Arg752Gln Pathogenic ★★ same type
- UNC45B p.Ala626Gly Uncertain significance ★★ ⚠ same type
- UNC45B p.Arg481Cys Uncertain significance ★★ ⚠ same type
- UNC45B p.Arg622Gln Uncertain significance ★★ ⚠ same type
- UNC45B p.Arg713Gly Uncertain significance ★★ ⚠ same type
- UNC45B p.Arg752Trp Uncertain significance ★★ ⚠ same type
- UNC45B p.Asp496Val Uncertain significance ★★ ⚠ same type
- UNC45B p.Asp902Glu 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/unc45b-p-leu596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown