UNC45B p.Glu255=
c.765G>A · rs371424117 · VCV2717410
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0567%, 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 0.73 | GERP 0.88, phastCons 1 |
| Overall | ||
| CADD | 5.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0567%
Admixed American · 34/60,004 alleles
Filtering AF
0.0416%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0365%
Overall
0.0203%
327/1,614,058 alleles · ultra-rare
exomes 302/1,461,874 · genomes 25/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0567% | 1,765 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,472 |
| European (non-Finnish) | 0.0221% | 4,521 |
| African / African-American | 0.00934% | 10,703 |
| South Asian | 0.00549% | 18,217 |
| Finnishnot grpmax-eligible | 0.00312% | 32,016 |
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.Glu255=
- Coding
- c.765G>A
- MANE Select
- NM_001267052
- dbSNP
- rs371424117
- Type
- single nucleotide variant
- Location
- chr17:35155421 (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-glu255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown