UMPS p.Phe58=
c.174C>T · rs539724738 · VCV3052374
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0367%, amr)
Conditions
1
UMPS-related disorder
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 -0.43 | GERP -4.8, phastCons 0.078 |
| Overall | ||
| CADD | 7.532 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0367%
Admixed American · 22/60,008 alleles
Filtering AF
0.0248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.00198%
32/1,613,788 alleles · ultra-rare
exomes 12/1,461,476 · genomes 20/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0367% | 2,728 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,812 |
| Finnishnot grpmax-eligible | 0.00156% | 63,986 |
| European (non-Finnish) | 8.48e-05% | 1,179,810 |
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
- UMPS
- Protein
- p.Phe58=
- Coding
- c.174C>T
- MANE Select
- NM_000373
- dbSNP
- rs539724738
- Type
- single nucleotide variant
- Location
- chr3:124735110 (GRCh38)
- Gene constraint
- LOEUF 0.735 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.36 · 125 PDB
- Residue 58
- the 'oprtase' region; an α-helix
Disease context
UMPS-related disorder
Similar variants
- UMPS p.Arg230Cys Uncertain significance ★★ same condition
- UMPS p.Asn433= Likely benign same condition
- UMPS p.Thr175= Likely benign same condition
- UMPS c.*37C>T Uncertain significance ★★ same type
- UMPS p.Ala386= Uncertain significance ★★ same type
- UMPS p.Ala386Val Uncertain significance ★★ ⚠ same type
- UMPS p.Ala4Pro Uncertain significance ★★ ⚠ same type
- UMPS p.Arg313Trp 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/umps-p-phe58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown