NAGLU p.Val439fs
c.1314_1315insC · VCV4818037
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
mucopolysaccharidosis type 3B
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5.6 | GERP 2.4, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- NAGLU
- Protein
- p.Val439fs
- Coding
- c.1314_1315insC
- MANE Select
- NM_000263
- Type
- Insertion
- Location
- chr17:42543320 (GRCh38)
- Gene constraint
- LOEUF 1.029 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.19 · 1 PDB
- Residue 439
- a β-strand; a UniProt-annotated variant site (in mps3b)
Disease context
mucopolysaccharidosis type 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Mucopolysaccharidosis type 3 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood
- Prevalence
- 1-9 / 1 000 000 (Brazil)
Similar variants
- NAGLU c.1021+1G>A Likely pathogenic ★★ same condition
- NAGLU c.1022-2A>G Pathogenic/Likely pathogenic ★★ same condition
- NAGLU c.383+1G>T Pathogenic/Likely pathogenic ★★ same condition
- NAGLU c.384-1G>A Pathogenic ★★ same condition
- NAGLU c.531+1G>A Pathogenic ★★ same condition
- NAGLU c.531+1G>C Pathogenic ★★ same condition
- NAGLU c.678+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NAGLU p.Arg130Cys 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/naglu-p-val439fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown