Is UROD p.Ala80= (c.240T>G) pathogenic?

UROD p.Ala80= (c.240T>G) is classified Uncertain significance in UROD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with familial porphyria cutanea tarda.

What condition is associated with UROD p.Ala80= (c.240T>G)?

UROD p.Ala80= (c.240T>G) is associated with familial porphyria cutanea tarda (ClinVar).

How common is UROD p.Ala80= (c.240T>G) in the general population?

UROD p.Ala80= (c.240T>G) is absent from gnomAD v4.1 (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.Ala80=

c.240T>G · rs1644820833 · VCV874338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial porphyria cutanea tarda

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.036	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 1.8, phastCons 1
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UROD
Protein: p.Ala80=
Coding: c.240T>G
MANE Select: NM_000374
dbSNP: rs1644820833
Type: single nucleotide variant
Location: chr1:45013318 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 19 PDB
Residue 80: a UniProt-annotated variant site (in hep); a UniProt-annotated variant site (in fpct; decrease of activity)

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.Ala80Ser Pathogenic/Likely pathogenic ★★ ⚠ same residue
UROD p.Ala80Gly Pathogenic ★ ⚠ same residue
UROD p.Ala80Thr Uncertain significance ★ ⚠ same residue
UROD p.Ala80Val 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

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-ala80 (accessed [today's date]).

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