Is UROD p.Arg142Ter (c.424C>T) pathogenic?

UROD p.Arg142Ter (c.424C>T) is classified Pathogenic/Likely pathogenic in UROD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Very rare (popmax 0.00229%, nfe); Associated with familial porphyria cutanea tarda.

What condition is associated with UROD p.Arg142Ter (c.424C>T)?

UROD p.Arg142Ter (c.424C>T) is associated with familial porphyria cutanea tarda (ClinVar).

How common is UROD p.Arg142Ter (c.424C>T) in the general population?

UROD p.Arg142Ter (c.424C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

How is Porphyria cutanea tarda inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

UROD p.Arg142Ter

c.424C>T · rs780227281 · VCV1436524

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Conditions

familial porphyria cutanea tarda

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
REVEL	0.108	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,180,012 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00173% 28/1,614,012 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,704
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Arg142Ter
Coding: c.424C>T
MANE Select: NM_000374
dbSNP: rs780227281
Type: single nucleotide variant
Location: chr1:45013741 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 19 PDB
Residue 142: a UniProt-annotated variant site (in fpct); an α-helix

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

Disease context

familial porphyria cutanea tarda — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Porphyria cutanea tarda (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

UROD p.Arg142Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
UROD c.636+1G>C 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
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-arg142ter (accessed [today's date]).

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