FUS p.Tyr100=
c.300T>C · rs376424892 · VCV1539279
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Conditions
3
Inborn genetic diseases
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 -0.15 | GERP -0.056, phastCons 0.74 |
| Overall | ||
| CADD | 9.643 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00409%
66/1,613,962 alleles · ultra-rare
exomes 60/1,461,712 · genomes 6/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| European (non-Finnish) | 0.00517% | 19,342 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,498 |
| South Asian | 0.0011% | 91,066 |
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
- FUS
- Protein
- p.Tyr100=
- Coding
- c.300T>C
- MANE Select
- NM_004960
- dbSNP
- rs376424892
- Type
- single nucleotide variant
- Location
- chr16:31183967 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.96 · 23 PDB
- Residue 100
- the 'disordered' region; a turn
Similar variants
- FUS p.Arg481Ter Pathogenic/Likely pathogenic ★★ same condition
- FUS p.Arg495Ter Pathogenic ★★ same condition
- FUS p.Arg514Gly Pathogenic ★★ ⚠ same condition
- FUS p.Arg521Cys Pathogenic ★★ same condition
- FUS p.Arg521Gly Pathogenic ★★ same condition
- FUS p.Arg521His Pathogenic ★★ ⚠ same condition
- FUS p.Arg521Leu Pathogenic/Likely pathogenic ★★ same condition
- FUS p.Lys510Glu 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/fus-p-tyr100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown