UNC45A p.Cys596=
c.1788C>T · rs35027972 · VCV1170773
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.24%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.23 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.29 | GERP -0.045, phastCons 0.16 |
| Overall | ||
| CADD | 14.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.24%
African / African-American · 1,680/74,966 alleles
Filtering AF
2.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.12%
Overall
0.113%
1,825/1,613,980 alleles · low-frequency
exomes 906/1,461,820 · genomes 919/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.24% | 45 |
| Remaining individualsnot grpmax-eligible | 0.112% | 893 |
| Admixed American | 0.095% | 1,053 |
| Middle Eastern | 0.0826% | 1,210 |
| South Asian | 0.0011% | 91,072 |
| European (non-Finnish) | 0.00102% | 98,334 |
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.Cys596=
- Coding
- c.1788C>T
- MANE Select
- NM_018671
- dbSNP
- rs35027972
- Type
- single nucleotide variant
- Location
- chr15:90948704 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.36 · 1 PDB
- Residue 596
- 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-cys596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown