FUS p.Phe375=
c.1125T>C · rs1467894155 · VCV2047639
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
2
tremor, hereditary essential, 4
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 0.27 | GERP -1.2, phastCons 0.98 |
| Overall | ||
| CADD | 8.937 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,974 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000248%
4/1,614,012 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,987 |
| East Asian | 0.00223% | 44,904 |
| European (non-Finnish) | 8.47e-05% | 1,180,011 |
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.Phe375=
- Coding
- c.1125T>C
- MANE Select
- NM_004960
- dbSNP
- rs1467894155
- Type
- single nucleotide variant
- Location
- chr16:31190098 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.96 · 23 PDB
- Residue 375
- an α-helix; the 'disordered' region
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-phe375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown