USB1 p.His84=
c.252C>T · rs147246452 · VCV1547394
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, afr)
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 -7.1 | GERP -3.3 |
| Overall | ||
| CADD | 10.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,888 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.00105%
17/1,613,726 alleles · ultra-rare
exomes 14/1,461,634 · genomes 3/152,092 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0107% | 9,361 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| Finnishnot grpmax-eligible | 0.00157% | 63,802 |
| European (non-Finnish) | 0.000508% | 196,670 |
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
- USB1
- Protein
- p.His84=
- Coding
- c.252C>T
- MANE Select
- NM_024598
- dbSNP
- rs147246452
- Type
- single nucleotide variant
- Location
- chr16:58002632 (GRCh38)
- Gene constraint
- LOEUF 1.016 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 83.91 · 5 PDB
- Residue 84
- a β-strand
Similar variants
- USB1 c.266-1G>A Pathogenic ★★ same type
- USB1 p.His208Arg Likely pathogenic ★★ same type
- USB1 p.Ala106Ser Uncertain significance ★★ ⚠ same type
- USB1 p.Ala218Thr Uncertain significance ★★ ⚠ same type
- USB1 p.Ala218Val Uncertain significance ★★ ⚠ same type
- USB1 p.Arg112Gln Uncertain significance ★★ ⚠ same type
- USB1 p.Arg112Trp Uncertain significance ★★ ⚠ same type
- USB1 p.Arg130Cys 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/usb1-p-his84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown