GUSB p.Pro108Leu
c.323C>T · rs1268678201 · VCV930289
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5026 | ambiguous |
|---|---|---|
| REVEL | 0.92 | moderately pathogenic-leaning |
| SaProt | LLR -12.91 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.6 | GERP 0.58, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 6,069 bp · p 0.83 · regional, not allelic |
| Overall | ||
| CADD | 24.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0173% | 5,796 |
| Admixed Americangrpmax | 0.00336% | 29,771 |
| African / African-American | 0.00134% | 74,524 |
| South Asian | 0.0011% | 90,940 |
| European (non-Finnish) | 0.000678% | 147,430 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- GUSB
- Protein
- p.Pro108Leu
- Coding
- c.323C>T
- MANE Select
- NM_000181
- dbSNP
- rs1268678201
- Type
- single nucleotide variant
- Location
- chr7:65980297 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.35 · 2 PDB
- Residue 108
- an α-helix
Disease context
mucopolysaccharidosis type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Mucopolysaccharidosis type 7 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Antenatal, Childhood, Infancy, Neonatal
- Prevalence
- <1 / 1 000 000 (Europe)
Similar variants
- GUSB p.Pro108= Conflicting classifications of pathogenicity ★ same residue
- GUSB c.1244+1G>A Pathogenic ★★ same condition
- GUSB c.581+1G>A Pathogenic/Likely pathogenic ★★ same condition
- GUSB c.724+1G>T Pathogenic/Likely pathogenic ★★ same condition
- GUSB p.Ala619Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- GUSB p.Arg110Ter Pathogenic/Likely pathogenic ★★ same condition
- GUSB p.Arg167Ter Pathogenic/Likely pathogenic ★★ same condition
- GUSB p.Arg216Trp Pathogenic/Likely pathogenic ★★ same condition
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/gusb-p-pro108leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown