UNC45B p.Ala299=
c.897G>A · VCV4872290
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, amr)
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 -4.2 | GERP -3.7 |
| Overall | ||
| CADD | 7.635 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/59,994 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00785%
Overall
0.00743%
120/1,613,992 alleles · ultra-rare
exomes 99/1,461,868 · genomes 21/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,454 |
| Middle Eastern | 0.0164% | 6,084 |
| African / African-American | 0.00801% | 12,484 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| European (non-Finnish) | 0.00788% | 12,688 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
| East Asian | 0.00223% | 44,896 |
| South Asian | 0.0011% | 91,076 |
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.Ala299=
- Coding
- c.897G>A
- MANE Select
- NM_001267052
- Type
- single nucleotide variant
- Location
- chr17:35159463 (GRCh38)
- Gene constraint
- LOEUF 0.969 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.38
Similar variants
- UNC45B p.Ala299Val Uncertain significance ★ ⚠ same residue
- 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
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-ala299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown