Is MOCOS p.Ser241Phe (c.722C>T) pathogenic?

MOCOS p.Ser241Phe (c.722C>T) is classified Uncertain significance in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely pathogenic (0.6898); Very rare (popmax 0.0011%, sas); Associated with xanthinuria type II.

What condition is associated with MOCOS p.Ser241Phe (c.722C>T)?

MOCOS p.Ser241Phe (c.722C>T) is associated with xanthinuria type II (ClinVar).

How common is MOCOS p.Ser241Phe (c.722C>T) in the general population?

MOCOS p.Ser241Phe (c.722C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Hereditary xanthinuria inherited?

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

What do computational predictors say about MOCOS p.Ser241Phe (c.722C>T)?

AlphaMissense predicts likely pathogenic (score 0.6898) — an in-silico prediction, not a clinical call.

MOCOS p.Ser241Phe

c.722C>T · VCV3583265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

xanthinuria type II

Computational evidence

Protein change
AlphaMissense	0.6898	likely pathogenic
REVEL	0.43	indeterminate
SaProt	LLR -12.00	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.1, phastCons 0.9
Regional constraint	o/e 0.99	unconstrained · MANE · 81 kb · p 0.84 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	0.000169%	590,012

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.Ser241Phe
Coding: c.722C>T
MANE Select: NM_017947
Type: single nucleotide variant
Location: chr18:36200105 (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-ser241phe (accessed [today's date]).

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