USP8 p.Arg250=
c.748A>C · rs746090450 · VCV978489
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00373%, 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 4.2 | GERP 0.97, phastCons 1 |
| Overall | ||
| CADD | 11.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00373%
European (non-Finnish) · 44/1,179,998 alleles
Filtering AF
0.00283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00252%
Overall
0.00279%
45/1,613,930 alleles · very rare
exomes 43/1,461,780 · genomes 2/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00373% | 26,818 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
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
- USP8
- Protein
- p.Arg250=
- Coding
- c.748A>C
- MANE Select
- NM_005154
- dbSNP
- rs746090450
- Type
- single nucleotide variant
- Location
- chr15:50471694 (GRCh38)
- Gene constraint
- LOEUF 0.28 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.98 · 9 PDB
- Residue 250
- the rhodanese domain; a turn
Similar variants
- USP8 p.Arg133Trp Uncertain significance ★★ ⚠ same type
- USP8 p.Phe875Ser Uncertain significance ★★ ⚠ same type
- USP8 p.Pro703His Uncertain significance ★★ ⚠ same type
- USP8 c.104+16C>T Benign ★★ same type
- USP8 c.250-8A>C Benign ★★ same type
- USP8 c.-58G>C Benign ★★ same type
- USP8 p.Ala348Thr Benign ★★ same type
- USP8 p.Arg483Gln Benign ★★ 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/usp8-p-arg250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown