USP53 p.Asp108=
c.324T>C · VCV4968354
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.34 | GERP -4.8, phastCons 0.29 |
| Overall | ||
| CADD | 8.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,028 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,168 alleles · very rare
exomes 2/1,461,816 · genomes 0/152,352 · joint denominator
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
- USP53
- Protein
- p.Asp108=
- Coding
- c.324T>C
- MANE Select
- NM_001371395
- Type
- single nucleotide variant
- Location
- chr4:119248834 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.34
- Residue 108
- the usp domain; a UniProt-annotated variant site (in pfic7)
Similar variants
- USP53 p.Arg111Ter Likely pathogenic ★★ same type
- USP53 p.Arg338Ter Pathogenic ★★ same type
- USP53 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same type
- USP53 p.Arg520Ter Pathogenic ★★ same type
- USP53 p.Arg582Ter Pathogenic/Likely pathogenic ★★ same type
- USP53 p.Arg58Gln Uncertain significance ★★ ⚠ same type
- USP53 p.Asn97Asp Uncertain significance ★★ ⚠ same type
- USP53 p.Asn97Ser Uncertain significance ★★ ⚠ 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/usp53-p-asp108 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown