Is UMOD p.Pro280= (c.840C>T) pathogenic?

UMOD p.Pro280= (c.840C>T) is classified Benign/Likely benign in UMOD (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-20). Common (popmax 5.75%, afr) — too common for a highly-penetrant pathogenic allele; Associated with kidney disorder.

What condition is associated with UMOD p.Pro280= (c.840C>T)?

UMOD p.Pro280= (c.840C>T) is associated with kidney disorder, familial juvenile hyperuricemic nephropathy type 1 (ClinVar).

UMOD p.Pro280=

Q: How common is UMOD p.Pro280= (c.840C>T) in the general population?

UMOD p.Pro280= (c.840C>T) is common (popmax 5.75%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.840C>T · rs78691203 · VCV196362

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.75%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

kidney disorder

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 -7.7	GERP -5
Overall
CADD	1.449	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.75% African / African-American · 4,317/75,052 alleles

Filtering AF 5.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.55%

Overall 0.362% 5,846/1,613,124 alleles · common exomes 3,226/1,460,782 · genomes 2,620/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.75%	17
Ashkenazi Jewishnot grpmax-eligible	1.86%	54
Remaining individualsnot grpmax-eligible	0.573%	175
Admixed American	0.47%	213
Middle Eastern	0.281%	356
European (non-Finnish)	0.0258%	3,869
South Asian	0.0154%	6,504
East Asian	0.00446%	22,437

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.Pro280=
Coding: c.840C>T
MANE Select: NM_003361
dbSNP: rs78691203
Type: single nucleotide variant
Location: chr16:20348461 (GRCh38)
Gene constraint: LOEUF 1.241 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 10 PDB
Residue 280: the d10c domain

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

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial juvenile hyperuricemic nephropathy type 1

Similar variants

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
UMOD p.Cys112Tyr Pathogenic/Likely pathogenic ★★ same condition
UMOD p.Cys120Arg Likely pathogenic ★★ same condition
UMOD p.Cys248Trp 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-pro280 (accessed [today's date]).

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