Is UMOD p.Arg178Pro (c.533G>C) pathogenic?

UMOD p.Arg178Pro (c.533G>C) is classified Conflicting classifications of pathogenicity in UMOD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-30). AlphaMissense: ambiguous (0.3483); Absent from gnomAD v4.1; Associated with familial juvenile hyperuricemic nephropathy type 1.

What condition is associated with UMOD p.Arg178Pro (c.533G>C)?

UMOD p.Arg178Pro (c.533G>C) is associated with familial juvenile hyperuricemic nephropathy type 1 (ClinVar).

How common is UMOD p.Arg178Pro (c.533G>C) in the general population?

UMOD p.Arg178Pro (c.533G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UMOD p.Arg178Pro (c.533G>C)?

AlphaMissense predicts ambiguous (score 0.3483) — an in-silico prediction, not a clinical call.

UMOD p.Arg178Pro

c.533G>C · rs1228791562 · VCV586921

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3483 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial juvenile hyperuricemic nephropathy type 1

Computational evidence

Protein change
AlphaMissense	0.3483	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -11.49	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.7	GERP -5.4
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.0029 · regional, not allelic
Overall
CADD	0.37	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: UMOD
Protein: p.Arg178Pro
Coding: c.533G>C
MANE Select: NM_003361
dbSNP: rs1228791562
Type: single nucleotide variant
Location: chr16:20348768 (GRCh38)
Gene constraint: LOEUF 1.241 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 10 PDB
Residue 178: the d10c domain

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

Disease context

familial juvenile hyperuricemic nephropathy type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UMOD p.Arg178Leu Uncertain significance ★ ⚠ same residue
UMOD p.Arg178His Uncertain significance ★★ ⚠ same residue
UMOD p.Arg178Gly Uncertain significance ★ ⚠ same residue
UMOD p.Ala285Glu Pathogenic ★★ same condition
UMOD p.Ala461Glu Likely pathogenic ★★ same condition
UMOD p.Arg185Cys Pathogenic ★★ same condition
UMOD p.Arg204Gly Pathogenic/Likely pathogenic ★★ same condition
UMOD p.Cys106Tyr 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/umod-p-arg178pro (accessed [today's date]).

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