UNC45B p.Arg729=
c.2187G>A · rs138507624 · VCV740572
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0244%, afr)
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 4.4 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 10.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0244%
African / African-American · 18/73,636 alleles
Filtering AF
0.0157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.013%
Overall
0.00249%
39/1,567,232 alleles · ultra-rare
exomes 26/1,415,102 · genomes 13/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0244% | 4,091 |
| Remaining individualsnot grpmax-eligible | 0.0198% | 5,060 |
| East Asian | 0.0189% | 5,283 |
| Admixed American | 0.00187% | 53,612 |
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.Arg729=
- Coding
- c.2187G>A
- MANE Select
- NM_001267052
- dbSNP
- rs138507624
- Type
- single nucleotide variant
- Location
- chr17:35177542 (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-arg729 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown