UNC45A p.Glu449=
c.1347G>A · rs151134605 · VCV1558504
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0549%, sas)
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 |
|---|---|---|
| Pangolin | Δ0.35 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -4.1, phastCons 1 |
| Overall | ||
| CADD | 13.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0549%
South Asian · 50/91,090 alleles
Filtering AF
0.0427%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0385%
Overall
0.00508%
82/1,614,046 alleles · ultra-rare
exomes 66/1,461,784 · genomes 16/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0549% | 1,822 |
| African / African-American | 0.0307% | 3,259 |
| Middle Eastern | 0.0166% | 6,008 |
| Admixed American | 0.005% | 20,005 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,824 |
| European (non-Finnish) | 0.000169% | 590,030 |
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.Glu449=
- Coding
- c.1347G>A
- MANE Select
- NM_018671
- dbSNP
- rs151134605
- Type
- single nucleotide variant
- Location
- chr15:90946761 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.36 · 1 PDB
- Residue 449
- 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-glu449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown