MAN2B1 p.Arg950Pro
c.2849G>C · rs139041112 · VCV208279
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4679 | ambiguous |
|---|---|---|
| REVEL | 0.571 | indeterminate |
| SaProt | LLR -12.68 | damaging |
| Splicing | ||
| SpliceAI | Δ0.30 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -3.2 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 20 kb · p 0.03 · regional, not allelic |
| Overall | ||
| CADD | 18.53 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
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
- MAN2B1
- Protein
- p.Arg950Pro
- Coding
- c.2849G>C
- MANE Select
- NM_000528
- dbSNP
- rs139041112
- Type
- single nucleotide variant
- Location
- chr19:12647307 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.78
- Residue 950
- a UniProt-annotated variant site (in mansa); a UniProt-annotated variant site (in mansa; uncertain significance); a UniProt-annotated variant site (in mansa; results in less than 20% of wild-type enzyme activity; protein localizes to the lysosome; when associated in cis with s-501; abolishes proteolytic cleavage of the protein; abolishes secretion of the protein; protein retained in the endoplasmic reticulum)
Disease context
alpha-mannosidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Alpha-mannosidosis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- MAN2B1 p.Arg950His Uncertain significance ★★ ⚠ same residue
- MAN2B1 p.Arg950= Likely benign ★ same residue
- MAN2B1 c.1026+2T>G Pathogenic/Likely pathogenic ★★ same condition
- MAN2B1 c.1109+1G>C Pathogenic/Likely pathogenic ★★ same condition
- MAN2B1 c.1527+1G>A Likely pathogenic ★★ same condition
- MAN2B1 c.1527+1G>T Pathogenic/Likely pathogenic ★★ same condition
- MAN2B1 c.1527+2T>G Pathogenic ★★ same condition
- MAN2B1 c.1528-1G>A 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/man2b1-p-arg950pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown