Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.38%, eas)
Conditions
1
familial porphyria cutanea tarda
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.292 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -2.9 |
| Overall | ||
| CADD | 5.723 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.38%
East Asian · 619/44,890 alleles
Filtering AF
1.29%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.25%
Overall
0.636%
10,260/1,614,164 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.38% | 73 |
| Finnishnot grpmax-eligible | 1.17% | 85 |
| European (non-Finnish) | 0.703% | 142 |
| Remaining individualsnot grpmax-eligible | 0.477% | 210 |
| Admixed American | 0.27% | 371 |
| African / African-American | 0.101% | 988 |
| Middle Eastern | 0.099% | 1,010 |
| South Asian | 0.0549% | 1,822 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
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
- UROD
- Protein
- p.Pro150=
- Coding
- c.450G>A
- MANE Select
- NM_000374
- dbSNP
- rs2234479
- Type
- single nucleotide variant
- Location
- chr1:45013767 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 96.90 · 19 PDB
Disease context
familial porphyria cutanea tarda — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Porphyria cutanea tarda (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial
- Onset
- Adult
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- UROD p.Pro150Leu Uncertain significance ★ ⚠ same residue
- UROD c.636+1G>C Pathogenic ★★ same condition
- UROD p.Arg142Ter Pathogenic/Likely pathogenic ★★ same condition
- UROD p.Arg193Pro Likely pathogenic ★★ same condition
- UROD p.Gln116Ter Pathogenic ★★ same condition
- UROD p.Gln206Ter Pathogenic/Likely pathogenic ★★ same condition
- UROD p.Glu314= Pathogenic/Likely pathogenic ★★ same condition
- UROD p.Gly281Val Pathogenic/Likely pathogenic ★★ same condition
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/urod-p-pro150 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown