Is UROD p.Arg193Pro (c.578G>C) pathogenic?

UROD p.Arg193Pro (c.578G>C) is classified Likely pathogenic in UROD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-10). AlphaMissense: likely pathogenic (0.8321); Very rare (popmax 0.000169%, nfe); Associated with UROD-related disorder.

What condition is associated with UROD p.Arg193Pro (c.578G>C)?

UROD p.Arg193Pro (c.578G>C) is associated with UROD-related disorder, familial porphyria cutanea tarda (ClinVar).

How common is UROD p.Arg193Pro (c.578G>C) in the general population?

UROD p.Arg193Pro (c.578G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about UROD p.Arg193Pro (c.578G>C)?

AlphaMissense predicts likely pathogenic (score 0.8321) — an in-silico prediction, not a clinical call.

UROD p.Arg193Pro

c.578G>C · rs143823335 · VCV254172

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

UROD-related disorder

Computational evidence

Protein change
AlphaMissense	0.8321	likely pathogenic ✓ concordant with ClinVar
REVEL	0.669	pathogenic-leaning
SaProt	LLR -14.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.061	GERP -2.8
Regional constraint	o/e 0.81	unconstrained · MANE · 3,229 bp · p 2.9e-05 · regional, not allelic
Overall
CADD	19.13	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,210 alleles · very rare exomes 2/1,461,888 · genomes 0/152,322 · joint denominator

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.Arg193Pro
Coding: c.578G>C
MANE Select: NM_000374
dbSNP: rs143823335
Type: single nucleotide variant
Location: chr1:45014012 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 19 PDB
Residue 193: a UniProt-annotated variant site (in fpct; insoluble protein); an α-helix

Full UROD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UROD-related disorder

Also linked: familial porphyria cutanea tarda

Similar variants

UROD p.Arg193His Uncertain significance ★ ⚠ same residue
UROD c.636+1G>C Pathogenic ★★ same condition
UROD p.Arg142Ter Pathogenic/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
UROD p.Met165Arg 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-arg193pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown