UNC45A p.Cys258=
c.774C>T · rs148133490 · VCV1554181
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.114%, nfe)
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 2.2 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 13.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.114%
European (non-Finnish) · 1,348/1,180,050 alleles
Filtering AF
0.109%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.107%
Overall
0.0888%
1,434/1,614,096 alleles · rare
exomes 1,362/1,461,882 · genomes 72/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.114% | 875 |
| Remaining individualsnot grpmax-eligible | 0.0592% | 1,689 |
| Admixed American | 0.05% | 2,000 |
| Middle Eastern | 0.0493% | 2,028 |
| African / African-American | 0.0133% | 7,493 |
| Finnishnot grpmax-eligible | 0.00625% | 16,009 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| South Asian | 0.0011% | 91,086 |
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.Cys258=
- Coding
- c.774C>T
- MANE Select
- NM_018671
- dbSNP
- rs148133490
- Type
- single nucleotide variant
- Location
- chr15:90942523 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.36 · 1 PDB
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-cys258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown