FUS p.Arg498fs
c.1490dup · VCV4929593
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
FUS-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 14 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 8 | GERP 1.2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- FUS
- Protein
- p.Arg498fs
- Coding
- c.1490dup
- MANE Select
- NM_004960
- Type
- Duplication
- Location
- chr16:31191054 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.96 · 23 PDB
- Residue 498
- the 'disordered' region; a modified residue (asymmetric dimethylarginine)
Disease context
FUS-related disorder
Similar variants
- FUS p.Arg498Gln Uncertain significance ★★ same residue
- FUS c.*103dup Uncertain significance ★ same condition
- FUS p.Arg498Gly Uncertain significance ★ ⚠ same residue
- FUS c.1542-6_1542-5dup Benign same condition
- FUS p.Arg495Ter Pathogenic ★★ same condition
- FUS p.Pro525Leu Pathogenic ★★ same condition
- FUS p.Gln210His Uncertain significance ★★ ⚠ same condition
- FUS p.Gly217Arg Uncertain significance ★★ ⚠ 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/fus-p-arg498fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown