Is UMOD p.Arg185= (c.555C>T) pathogenic?

UMOD p.Arg185= (c.555C>T) is classified Likely benign in UMOD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-27). Ultra-rare (popmax 0.0174%, mid); Associated with familial juvenile hyperuricemic nephropathy type 1.

What condition is associated with UMOD p.Arg185= (c.555C>T)?

UMOD p.Arg185= (c.555C>T) is associated with familial juvenile hyperuricemic nephropathy type 1 (ClinVar).

How common is UMOD p.Arg185= (c.555C>T) in the general population?

UMOD p.Arg185= (c.555C>T) is ultra-rare (popmax 0.0174%, mid) (gnomAD).

UMOD p.Arg185=

c.555C>T · rs866510195 · VCV1541858

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, mid)

Conditions

familial juvenile hyperuricemic nephropathy type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.004	GERP -5.4, phastCons 0.43
Overall
CADD	7.242	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% Middle Eastern · 1/5,744 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000259% 4/1,545,012 alleles · ultra-rare exomes 4/1,392,634 · genomes 0/152,378 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0174%	5,744
European (non-Finnish)	0.000262%	382,095

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: UMOD
Protein: p.Arg185=
Coding: c.555C>T
MANE Select: NM_003361
dbSNP: rs866510195
Type: single nucleotide variant
Location: chr16:20348746 (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.Arg185Gly Likely pathogenic ★ same residue
UMOD p.Arg185Pro 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-arg185 (accessed [today's date]).

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