MAN2B1 p.Arg950=
c.2850C>T · rs2145220436 · VCV1539307
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
alpha-mannosidosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP -0.8, phastCons 1 |
| Overall | ||
| CADD | 9.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- MAN2B1
- Protein
- p.Arg950=
- Coding
- c.2850C>T
- MANE Select
- NM_000528
- dbSNP
- rs2145220436
- Type
- single nucleotide variant
- Location
- chr19:12647306 (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.Arg950Pro Conflicting classifications of pathogenicity ★ 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-arg950 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown