Is UMOD p.Arg185Pro (c.554G>C) pathogenic?

UMOD p.Arg185Pro (c.554G>C) is classified Likely pathogenic in UMOD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-31). AlphaMissense: likely pathogenic (0.9627); Absent from gnomAD v4.1; Associated with familial juvenile hyperuricemic nephropathy type 1.

What condition is associated with UMOD p.Arg185Pro (c.554G>C)?

UMOD p.Arg185Pro (c.554G>C) is associated with familial juvenile hyperuricemic nephropathy type 1 (ClinVar).

How common is UMOD p.Arg185Pro (c.554G>C) in the general population?

UMOD p.Arg185Pro (c.554G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UMOD p.Arg185Pro (c.554G>C)?

AlphaMissense predicts likely pathogenic (score 0.9627) — an in-silico prediction, not a clinical call.

UMOD p.Arg185Pro

c.554G>C · VCV3578748

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial juvenile hyperuricemic nephropathy type 1

Computational evidence

Protein change
AlphaMissense	0.9627	likely pathogenic ✓ concordant with ClinVar · top 3% in UMOD
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -16.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.0029 · regional, not allelic
Overall
CADD	24.5	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.Arg185Pro
Coding: c.554G>C
MANE Select: NM_003361
Type: single nucleotide variant
Location: chr16:20348747 (GRCh38)
Gene constraint: LOEUF 1.241 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 10 PDB
Residue 185: the d10c domain; a UniProt-annotated variant site (in adtkd1)

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.Arg185Cys Pathogenic ★★ same residue
UMOD p.Arg185= Likely benign ★★ same residue
UMOD p.Arg185Gly Likely pathogenic ★ same residue
UMOD p.Arg185Ser Likely pathogenic ★ same residue
UMOD p.Arg185His Pathogenic ★ same residue
UMOD p.Ala285Glu Pathogenic ★★ same condition
UMOD p.Ala461Glu Likely pathogenic ★★ same condition
UMOD p.Arg204Gly 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-arg185pro (accessed [today's date]).

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