MANBA p.Thr609=
c.1827A>G · rs2476757965 · VCV2745037
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
beta-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 -0.17 | GERP 0.41, phastCons 0.015 |
| Overall | ||
| CADD | 7.192 | 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
- MANBA
- Protein
- p.Thr609=
- Coding
- c.1827A>G
- MANE Select
- NM_005908
- dbSNP
- rs2476757965
- Type
- single nucleotide variant
- Location
- chr4:102650579 (GRCh38)
- Gene constraint
- LOEUF 0.826 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.05
- Residue 609
- a disulfide bond; a UniProt-annotated variant site (in mansb; complete loss of enzyme activity)
Disease context
beta-mannosidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Beta-mannosidosis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- MANBA c.1112+1G>T Likely pathogenic ★★ same condition
- MANBA c.1231-1G>A Likely pathogenic ★★ same condition
- MANBA c.1704+1G>T Likely pathogenic ★★ same condition
- MANBA c.2158-2A>G Pathogenic ★★ same condition
- MANBA c.273-1G>A Likely pathogenic ★★ same condition
- MANBA c.378+1G>A Likely pathogenic ★★ same condition
- MANBA c.549+1G>A Likely pathogenic ★★ same condition
- MANBA c.550-1G>A 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/manba-p-thr609 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown