FUS p.Ser57del
c.167CTT[1] · rs777545405 · VCV1213403
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0281%, nfe)
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 · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 10.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0281%
European (non-Finnish) · 332/1,179,982 alleles
Filtering AF
0.0256%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0246%
Overall
0.0242%
390/1,614,176 alleles · ultra-rare
exomes 359/1,461,826 · genomes 31/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0281% | 3,554 |
| African / African-American | 0.0253% | 3,951 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| Admixed American | 0.0167% | 6,002 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.00878% | 11,385 |
| East Asian | 0.00668% | 14,962 |
| Finnishnot grpmax-eligible | 0.00312% | 32,023 |
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.Ser57del
- Coding
- c.167CTT[1]
- MANE Select
- NM_004960
- dbSNP
- rs777545405
- Type
- Microsatellite
- Location
- chr16:31182639 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.96 · 23 PDB
- Residue 57
- the 'disordered' region; a β-strand
Similar variants
- FUS p.Gln519fs Pathogenic ★★ same condition
- FUS p.Gly504fs Pathogenic ★★ same condition
- FUS p.Gly228_Gly231del Uncertain significance ★★ same condition
- FUS p.Ser165del Uncertain significance ★★ same condition
- FUS c.518_523del Benign/Likely benign ★★ same condition
- FUS c.521_523+3dupGAGGTG Benign/Likely benign ★★ same condition
- FUS p.Gly231del Likely benign ★★ same condition
- FUS p.Gly231dup Benign/Likely benign ★★ 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-ser57del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown