Is UROD p.Ser129Ter (c.385_386insAGT) pathogenic?

UROD p.Ser129Ter (c.385386insAGT) is classified Pathogenic in UROD (ClinVar, Single submitter, 2 submitters; last evaluated 2021-10-15). Very rare (popmax 8.47e-05%, nfe); Associated with sporadic porphyria cutanea tarda.

What condition is associated with UROD p.Ser129Ter (c.385_386insAGT)?

UROD p.Ser129Ter (c.385_386insAGT) is associated with sporadic porphyria cutanea tarda, hepatoerythropoietic porphyria (ClinVar).

How common is UROD p.Ser129Ter (c.385_386insAGT) in the general population?

UROD p.Ser129Ter (c.385_386insAGT) is very rare (popmax 8.47e-05%, 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.Ser129Ter

c.385_386insAGT · rs2148982720 · VCV1353137

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

sporadic 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
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.81	GERP 1.4, phastCons 0.98

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 6.84e-05% 1/1,461,842 alleles · very rare

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.Ser129Ter
Coding: c.385_386insAGT
MANE Select: NM_000374
dbSNP: rs2148982720
Type: Insertion
Location: chr1:45013701 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 19 PDB
Residue 129: an α-helix

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

Disease context

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

Also linked: hepatoerythropoietic porphyria

For Porphyria cutanea tarda (Orphanet):

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

Similar variants

UROD p.Ser129Pro Uncertain significance ★ ⚠ same residue
UROD p.Pro62Leu Pathogenic/Likely pathogenic ★★ same condition
UROD p.Glu167Lys Uncertain significance ★★ ⚠ same condition
UROD p.Gly281Glu Pathogenic ★ same condition
UROD p.Tyr311Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
UROD p.Arg292Gly 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-ser129ter (accessed [today's date]).

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