USP53 p.Ser940=
c.2820C>T · VCV4765937
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0374%, 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 -5.5 | GERP -3.6 |
| Overall | ||
| CADD | 0.352 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0374%
South Asian · 34/90,920 alleles
Filtering AF
0.0274%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0241%
Overall
0.00553%
89/1,610,574 alleles · ultra-rare
exomes 84/1,461,808 · genomes 5/148,766 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0374% | 2,674 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,607 |
| European (non-Finnish) | 0.00424% | 23,576 |
| African / African-American | 0.00136% | 73,614 |
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.Ser940=
- Coding
- c.2820C>T
- MANE Select
- NM_001371395
- Type
- single nucleotide variant
- Location
- chr4:119292809 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.34
- Residue 940
- 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-ser940 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown