USB1 p.Pro88=
c.264A>G · VCV3711149
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.24 | gain · loss 0.10 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.3 |
| Overall | ||
| CADD | 0.806 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/75,030 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000494%
Overall
0.000434%
7/1,613,774 alleles · very rare
exomes 7/1,461,530 · genomes 0/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 25,010 |
| European (non-Finnish) | 0.000339% | 294,989 |
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.Pro88=
- Coding
- c.264A>G
- MANE Select
- NM_024598
- Type
- single nucleotide variant
- Location
- chr16:58002644 (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 88
- a β-strand
Similar variants
- USB1 p.Pro88Arg Uncertain significance ★ same residue
- USB1 p.Pro88Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro88 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown