Is UROD p.Ala22Val (c.65C>T) pathogenic?

UROD p.Ala22Val (c.65C>T) is classified Likely pathogenic in UROD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-27). AlphaMissense: likely benign (0.2437); Absent from gnomAD v4.1; Associated with UROD-related disorder.

What condition is associated with UROD p.Ala22Val (c.65C>T)?

UROD p.Ala22Val (c.65C>T) is associated with UROD-related disorder (ClinVar).

How common is UROD p.Ala22Val (c.65C>T) in the general population?

UROD p.Ala22Val (c.65C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UROD p.Ala22Val (c.65C>T)?

AlphaMissense predicts likely benign (score 0.2437) — an in-silico prediction, not a clinical call.

UROD p.Ala22Val

c.65C>T · VCV4972112

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2437 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

UROD-related disorder

Computational evidence

Protein change
AlphaMissense	0.2437	likely benign ⚠ discordant with ClinVar
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -8.24	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 3,229 bp · p 2.9e-05 · regional, not allelic
Overall
CADD	24.9	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

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.Ala22Val
Coding: c.65C>T
MANE Select: NM_000374
Type: single nucleotide variant
Location: chr1:45012951 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 96.90 · 19 PDB
Residue 22: an α-helix

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

Disease context

UROD-related disorder

Similar variants

UROD p.Arg193Pro Likely pathogenic ★★ same condition
UROD c.133+1G>T Likely pathogenic ★ same condition
UROD c.943-1G>A Pathogenic ★ same condition
UROD p.Arg142Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
UROD p.Pro150Leu Uncertain significance ★ ⚠ same condition
UROD p.Pro91Thr Uncertain significance ★ ⚠ same condition
UROD p.Ala51Thr Uncertain significance ⚠ same condition
UROD p.Gly225= Likely benign 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-ala22val (accessed [today's date]).

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