MAN2B1 p.Pro263=
c.789G>A · rs149484019 · VCV711513
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.32 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -16 | GERP -3.6 |
| Overall | ||
| CADD | 0.511 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.122% | 822 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,683 |
| Middle Easterngrpmax | 0.0165% | 6,062 |
| Admixed American | 0.00833% | 12,000 |
| European (non-Finnish) | 0.00695% | 14,391 |
| East Asian | 0.00446% | 22,442 |
| South Asian | 0.00439% | 22,773 |
| African / African-American | 0.00267% | 37,519 |
Ashkenazi Jewish 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
- MAN2B1
- Protein
- p.Pro263=
- Coding
- c.789G>A
- MANE Select
- NM_000528
- dbSNP
- rs149484019
- Type
- single nucleotide variant
- Location
- chr19:12663437 (GRCh38)
- Gene constraint
- LOEUF 0.898 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.78
- Residue 263
- a UniProt-annotated variant site (in mansa); a UniProt-annotated variant site (in mansa; results in less than 20% of wild-type enzyme activity; protein localizes to the lysosome)
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.Pro263Leu Pathogenic/Likely pathogenic ★★ same residue
- MAN2B1 p.Pro263Ser Uncertain significance ★ 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-pro263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown