UNC45A p.Asp427=
c.1281C>T · rs949088045 · VCV2974137
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.013%, nfe)
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 -8.8 | GERP -4 |
| Overall | ||
| CADD | 4.158 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.013%
European (non-Finnish) · 153/1,179,938 alleles
Filtering AF
0.0113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0107%
Overall
0.00992%
160/1,612,610 alleles · ultra-rare
exomes 157/1,460,376 · genomes 3/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.013% | 7,712 |
| African / African-American | 0.00401% | 24,967 |
| South Asian | 0.0033% | 30,335 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,362 |
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
- UNC45A
- Protein
- p.Asp427=
- Coding
- c.1281C>T
- MANE Select
- NM_018671
- dbSNP
- rs949088045
- Type
- single nucleotide variant
- Location
- chr15:90946695 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.36 · 1 PDB
- Residue 427
- a UniProt-annotated variant site (in oohe; uncertain significance)
Similar variants
- UNC45A p.Ala214Val Uncertain significance ★★ ⚠ same type
- UNC45A p.Ala371Thr Uncertain significance ★★ ⚠ same type
- UNC45A p.Ala386Val Uncertain significance ★★ ⚠ same type
- UNC45A p.Ala428Thr Uncertain significance ★★ ⚠ same type
- UNC45A p.Ala592Val Uncertain significance ★★ ⚠ same type
- UNC45A p.Ala711Thr Uncertain significance ★★ ⚠ same type
- UNC45A p.Ala761Thr Uncertain significance ★★ ⚠ same type
- UNC45A p.Arg107Gly 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/unc45a-p-asp427 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown