USP53 p.Ser185=
c.555T>G · VCV4782120
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0223%, eas)
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 -0.47 | GERP -3, phastCons 0.1 |
| Overall | ||
| CADD | 9.192 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0223%
East Asian · 10/44,862 alleles
Filtering AF
0.012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00917%
Overall
0.00062%
10/1,614,014 alleles · ultra-rare
exomes 9/1,461,766 · genomes 1/152,248 · 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.Ser185=
- Coding
- c.555T>G
- MANE Select
- NM_001371395
- Type
- single nucleotide variant
- Location
- chr4:119256509 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.34
- Residue 185
- the usp domain; a UniProt-annotated variant site (in pfic7)
Similar variants
- USP53 p.Ser185Phe Uncertain significance ★★ ⚠ same residue
- 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
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-ser185 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown