FUS p.Pro525=
c.1575G>A · rs562371582 · VCV732645
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0549%, sas)
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 -1.5 | GERP -4 |
| Overall | ||
| CADD | 4.604 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0549%
South Asian · 50/91,012 alleles
Filtering AF
0.0427%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0385%
Overall
0.00416%
67/1,612,196 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0549% | 1,820 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,616 |
| Admixed American | 0.00334% | 29,905 |
| European (non-Finnish) | 0.000933% | 107,231 |
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.Pro525=
- Coding
- c.1575G>A
- MANE Select
- NM_004960
- dbSNP
- rs562371582
- Type
- single nucleotide variant
- Location
- chr16:31191432 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.96 · 23 PDB
- Residue 525
- the 'disordered' region; a UniProt-annotated variant site (in als6)
Similar variants
- FUS p.Pro525Leu Pathogenic ★★ same residue
- FUS p.Pro525Ser Likely pathogenic ★ same residue
- FUS p.Pro525Thr Pathogenic ★ same residue
- FUS p.Pro525Ala Uncertain significance ★ ⚠ same residue
- FUS p.Arg481Ter Pathogenic/Likely pathogenic ★★ same type
- FUS p.Arg495Ter Pathogenic ★★ same type
- FUS p.Arg514Gly Pathogenic ★★ ⚠ same type
- FUS p.Arg521Cys Pathogenic ★★ same type
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-pro525 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown