Is MOCOS p.Leu148Phe (c.442C>T) pathogenic?

MOCOS p.Leu148Phe (c.442C>T) is classified Uncertain significance in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-29). AlphaMissense: likely benign (0.3177); Absent from gnomAD v4.1; Associated with xanthinuria type II.

What condition is associated with MOCOS p.Leu148Phe (c.442C>T)?

MOCOS p.Leu148Phe (c.442C>T) is associated with xanthinuria type II (ClinVar).

How common is MOCOS p.Leu148Phe (c.442C>T) in the general population?

MOCOS p.Leu148Phe (c.442C>T) is absent from gnomAD v4.1 (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.Leu148Phe (c.442C>T)?

AlphaMissense predicts likely benign (score 0.3177) — an in-silico prediction, not a clinical call.

MOCOS p.Leu148Phe

c.442C>T · rs2144900693 · VCV1449065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

xanthinuria type II

Computational evidence

Protein change
AlphaMissense	0.3177	likely benign
REVEL	0.484	indeterminate
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 81 kb · p 0.84 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MOCOS
Protein: p.Leu148Phe
Coding: c.442C>T
MANE Select: NM_017947
dbSNP: rs2144900693
Type: single nucleotide variant
Location: chr18:36199825 (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-leu148phe (accessed [today's date]).

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