Is MOCOS p.Val209= (c.627C>G) pathogenic?

MOCOS p.Val209= (c.627C>G) is classified Likely benign in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). Ultra-rare (popmax 0.0107%, afr); Associated with xanthinuria type II.

What condition is associated with MOCOS p.Val209= (c.627C>G)?

MOCOS p.Val209= (c.627C>G) is associated with xanthinuria type II (ClinVar).

How common is MOCOS p.Val209= (c.627C>G) in the general population?

MOCOS p.Val209= (c.627C>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

How is Hereditary xanthinuria inherited?

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

MOCOS p.Val209=

c.627C>G · rs373636590 · VCV2726794

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

xanthinuria type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -2.3, phastCons 0.5
Overall
CADD	5.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/75,074 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000558% 9/1,614,250 alleles · ultra-rare exomes 3/1,461,886 · genomes 6/152,364 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,384
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Val209=
Coding: c.627C>G
MANE Select: NM_017947
dbSNP: rs373636590
Type: single nucleotide variant
Location: chr18:36200010 (GRCh38)
Gene constraint: LOEUF 1.19 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.88

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-val209 (accessed [today's date]).

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