Is MOCOS p.Val449Phe (c.1345G>T) pathogenic?

MOCOS p.Val449Phe (c.1345G>T) is classified Uncertain significance in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.1687); Very rare (popmax 0.000424%, nfe); Associated with xanthinuria type II.

What condition is associated with MOCOS p.Val449Phe (c.1345G>T)?

MOCOS p.Val449Phe (c.1345G>T) is associated with xanthinuria type II (ClinVar).

How common is MOCOS p.Val449Phe (c.1345G>T) in the general population?

MOCOS p.Val449Phe (c.1345G>T) is very rare (popmax 0.000424%, nfe) (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.Val449Phe (c.1345G>T)?

AlphaMissense predicts likely benign (score 0.1687) — an in-silico prediction, not a clinical call.

MOCOS p.Val449Phe

c.1345G>T · VCV3583289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xanthinuria type II

Computational evidence

Protein change
AlphaMissense	0.1687	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -11.09	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP 0.58, phastCons 0.12
Regional constraint	o/e 0.99	unconstrained · MANE · 81 kb · p 0.84 · regional, not allelic
Overall
CADD	19.44	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,970 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,962 alleles · very rare exomes 5/1,461,644 · genomes 0/152,318 · joint denominator

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.Val449Phe
Coding: c.1345G>T
MANE Select: NM_017947
Type: single nucleotide variant
Location: chr18:36215525 (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-val449phe (accessed [today's date]).

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