Is MOCOS p.Pro725= (c.2175T>G) pathogenic?

MOCOS p.Pro725= (c.2175T>G) is classified Likely benign in MOCOS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0587%, afr); Associated with xanthinuria type II.

What condition is associated with MOCOS p.Pro725= (c.2175T>G)?

MOCOS p.Pro725= (c.2175T>G) is associated with xanthinuria type II (ClinVar).

How common is MOCOS p.Pro725= (c.2175T>G) in the general population?

MOCOS p.Pro725= (c.2175T>G) is ultra-rare (popmax 0.0587%, afr) (gnomAD).

How is Hereditary xanthinuria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MOCOS p.Pro725=

c.2175T>G · rs151067903 · VCV1630553

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0587%, afr)

Conditions

xanthinuria type II

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 -0.18	GERP -1.2
Overall
CADD	2.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0587% African / African-American · 44/74,930 alleles

Filtering AF 0.0449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.00285% 46/1,613,780 alleles · ultra-rare exomes 21/1,461,560 · genomes 25/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0587%	1,703
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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: MOCOS
Protein: p.Pro725=
Coding: c.2175T>G
MANE Select: NM_017947
dbSNP: rs151067903
Type: single nucleotide variant
Location: chr18:36256978 (GRCh38)
Gene constraint: LOEUF 1.19 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.88
Residue 725: the mosc domain

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

Disease context

xanthinuria type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary xanthinuria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

MOCOS c.1218+1G>C Likely pathogenic ★★ same condition
MOCOS c.2164+2T>C Likely pathogenic ★★ same condition
MOCOS c.232+1G>A Likely pathogenic ★★ same condition
MOCOS p.Arg419Ter Pathogenic ★★ same condition
MOCOS p.Arg776Cys Pathogenic/Likely pathogenic ★★ same condition
MOCOS p.Gln516Ter Likely pathogenic ★★ same condition
MOCOS p.Glu42Ter Likely pathogenic ★★ same condition
MOCOS p.Glu763Ter 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/mocos-p-pro725 (accessed [today's date]).

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