Is OTC p.Val142fs (c.424_514del) pathogenic?

OTC p.Val142fs (c.424514del) is classified Likely pathogenic in OTC (ClinVar, Single submitter, 1 submitter). Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.Val142fs (c.424_514del)?

OTC p.Val142fs (c.424_514del) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How is Ornithine transcarbamylase deficiency inherited?

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

OTC p.Val142fs

c.424_514del · VCV3899348

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ornithine carbamoyltransferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: OTC
Protein: p.Val142fs
Coding: c.424_514del
MANE Select: NM_000531
Type: Deletion
Location: chrX:38401310 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB

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

Disease context

ornithine carbamoyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ornithine transcarbamylase deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

OTC p.Val142= Likely benign ★★ same residue
OTC p.Val142Gly Uncertain significance ★ ⚠ same residue
OTC c.299-8del Benign/Likely benign ★★ same condition
OTC c.718-2_731del Pathogenic ★ same condition
OTC p.Ala218fs Pathogenic ★ same condition
OTC p.Asn10fs Pathogenic ★ same condition
OTC p.Asn47fs Pathogenic ★ same condition
OTC p.Gln270fs 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/otc-p-val142fs (accessed [today's date]).

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