UNC45A p.Pro721=
c.2163G>A · rs16945050 · VCV1167287
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 20.8%, afr) — too common for a highly-penetrant pathogenic allele
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 -3.5 | GERP -4.1 |
| Overall | ||
| CADD | 2.517 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
20.8%
African / African-American · 15,208/73,126 alleles
Filtering AF
20.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 20.4%
Overall
1.14%
17,745/1,551,670 alleles · common
exomes 8,678/1,399,386 · genomes 9,067/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 20.8% | 5 |
| Admixed American | 1.78% | 56 |
| Remaining individualsnot grpmax-eligible | 1.54% | 65 |
| Middle Eastern | 1.32% | 76 |
| Ashkenazi Jewishnot grpmax-eligible | 0.15% | 666 |
| South Asian | 0.0547% | 1,827 |
| European (non-Finnish) | 0.0465% | 2,152 |
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.Pro721=
- Coding
- c.2163G>A
- MANE Select
- NM_018671
- dbSNP
- rs16945050
- Type
- single nucleotide variant
- Location
- chr15:90950243 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.36 · 1 PDB
- Residue 721
- a UniProt-annotated variant site (in oohe; uncertain significance)
Similar variants
- UNC45A p.Pro721Leu 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-pro721 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown