UNC45A p.Asp540=
c.1620C>T · rs375358237 · VCV1596609
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.178 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
African / African-American · 37/75,050 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0324%
Overall
0.00514%
83/1,614,124 alleles · ultra-rare
exomes 52/1,461,798 · genomes 31/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0493% | 2,028 |
| South Asian | 0.0242% | 4,140 |
| Middle Eastern | 0.0165% | 6,060 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
| Admixed American | 0.00833% | 12,004 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| East Asian | 0.00446% | 22,445 |
| European (non-Finnish) | 0.000847% | 118,004 |
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.Asp540=
- Coding
- c.1620C>T
- MANE Select
- NM_018671
- dbSNP
- rs375358237
- Type
- single nucleotide variant
- Location
- chr15:90948166 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.36 · 1 PDB
- Residue 540
- a UniProt-annotated variant site (in oohe; uncertain significance)
Similar variants
- UNC45A p.Asp540Asn Uncertain significance ★★ ⚠ same residue
- 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
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-asp540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown