UPB1 p.Pro84=
c.252C>T · rs944610975 · VCV2971816
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 -11 | GERP -2.8 |
| Overall | ||
| CADD | 0.546 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,028 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000496%
8/1,614,156 alleles · very rare
exomes 7/1,461,858 · genomes 1/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,014 |
| African / African-American | 0.00267% | 37,523 |
| East Asian | 0.00223% | 44,890 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| European (non-Finnish) | 0.000169% | 590,016 |
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
- UPB1
- Protein
- p.Pro84=
- Coding
- c.252C>T
- MANE Select
- NM_016327
- dbSNP
- rs944610975
- Type
- single nucleotide variant
- Location
- chr22:24500254 (GRCh38)
- Gene constraint
- LOEUF 0.982 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 97.10 · 2 PDB
- Residue 84
- the cn hydrolase domain
Similar variants
- UPB1 c.873+1G>A Pathogenic/Likely pathogenic ★★ same type
- UPB1 c.917-1G>A Pathogenic/Likely pathogenic ★★ same type
- UPB1 p.Asn345Ile Likely pathogenic ★★ same type
- UPB1 p.Gln118Ter Pathogenic ★★ same type
- UPB1 c.-27G>C Uncertain significance ★★ same type
- UPB1 p.Ala2Gly Uncertain significance ★★ ⚠ same type
- UPB1 p.Ala4Thr Uncertain significance ★★ ⚠ same type
- UPB1 p.Arg169Gln 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/upb1-p-pro84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown