USP53 p.Ser357fs
c.1069dup · VCV3370325
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
cholestasis, progressive familial intrahepatic, 7, with or without hearing loss
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 1.1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- USP53
- Protein
- p.Ser357fs
- Coding
- c.1069dup
- MANE Select
- NM_001371395
- Type
- Duplication
- Location
- chr4:119267413 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.34
- Residue 357
- a UniProt-annotated variant site (in pfic7)
Disease context
cholestasis, progressive familial intrahepatic, 7, with or without hearing loss — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Progressive familial intrahepatic cholestasis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Childhood, Infancy, Neonatal
Similar variants
- USP53 p.Ala27fs Likely pathogenic ★ same condition
- USP53 p.Ser357Cys Uncertain significance ★ ⚠ same residue
- USP53 c.145-10_168del Likely pathogenic ★★ same condition
- USP53 c.822+1del Likely pathogenic ★★ same condition
- USP53 p.Arg111Ter Likely pathogenic ★★ same condition
- USP53 p.Arg338Ter Pathogenic ★★ same condition
- USP53 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same condition
- USP53 p.Arg520Ter 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/usp53-p-ser357fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown