Is OTC p.Arg89del (c.264AAG[1]) pathogenic?

OTC p.Arg89del (c.264AAG[1]) is classified Uncertain significance in OTC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-26). No gnomAD frequency available for this variant; Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.Arg89del (c.264AAG[1])?

OTC p.Arg89del (c.264AAG[1]) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How common is OTC p.Arg89del (c.264AAG[1]) in the general population?

OTC p.Arg89del (c.264AAG[1]) is no gnomAD frequency available for this variant (gnomAD).

How is Ornithine transcarbamylase deficiency inherited?

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

OTC p.Arg89del

c.264AAG[1] · rs2068315148 · VCV957857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ornithine carbamoyltransferase deficiency

ClinGen expert panel — Urea Cycle Disorders VCEP

Uncertain Significance for ornithine carbamoyltransferase deficiency. Applied ACMG criteria (verbatim):

PM2_Supporting PM4

Curation rationale (ClinGen, verbatim)

The NM_000156.6:c.264AAG[1] (p.Arg89del) variant in OTC is an in-frame deletion of the Arg89 residue, which is located in the loop between the B3 beta-sheet and the H2 alpha-helix and is immediately adjacent to the STRT motif which is involved in carbamylphosphate binding and catalysis (PM4). This variant is absent in gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for OTC deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Urea Cycle Disorders Variant Curation Expert Panel (OTC specifications version 1.0.0): PM4, PM2_Supporting.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OTC
Protein: p.Arg89del
Coding: c.264AAG[1]
MANE Select: NM_000531
dbSNP: rs2068315148
Type: Microsatellite
Location: chrX:38369843 (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.Arg89fs Likely pathogenic ★ same residue
OTC p.Arg89Gly Uncertain significance ★★ ⚠ same residue
OTC p.Glu310del Pathogenic ★★ same condition
OTC p.Pro319del Uncertain significance ★★ same condition
OTC c.217-5TA[4] Likely benign ★★ same condition
OTC p.Glu273del Likely pathogenic ★ same condition
OTC c.298+2T>G Pathogenic ★★ same condition
OTC c.299-1G>A 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/otc-p-arg89del (accessed [today's date]).

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