SPSB3 p.Pro302=
c.906G>A · rs373221053 · VCV736496
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.025%, amr)
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 -15 | GERP -3.1 |
| Overall | ||
| CADD | 0.619 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.025%
Admixed American · 15/60,000 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.014%
Overall
0.014%
226/1,610,350 alleles · ultra-rare
exomes 215/1,458,088 · genomes 11/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.025% | 4,000 |
| European (non-Finnish) | 0.0166% | 6,020 |
| East Asian | 0.00891% | 11,223 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,608 |
| African / African-American | 0.00534% | 18,734 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,592 |
| Finnishnot grpmax-eligible | 0.00165% | 60,580 |
| South Asian | 0.0011% | 91,088 |
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
- SPSB3
- Protein
- p.Pro302=
- Coding
- c.906G>A
- MANE Select
- NM_080861
- dbSNP
- rs373221053
- Type
- single nucleotide variant
- Location
- chr16:1777259 (GRCh38)
- Gene constraint
- LOEUF 0.925 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.01 · 2 PDB
- Residue 302
- the socs box domain
Similar variants
- SPSB3 p.Ala115= Benign ★★ same type
- SPSB3 p.Ala18Val Uncertain significance ★ ⚠ same type
- SPSB3 p.Ala22Thr Uncertain significance ★ ⚠ same type
- SPSB3 p.Ala274Ser Uncertain significance ★ ⚠ same type
- SPSB3 p.Ala334Val Uncertain significance ★ ⚠ same type
- SPSB3 p.Ala337Thr Uncertain significance ★ ⚠ same type
- SPSB3 p.Arg20Gly Uncertain significance ★ ⚠ same type
- SPSB3 p.Arg269His 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/spsb3-p-pro302 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown