Is OTC p.Phe101fs (c.303del) pathogenic?

OTC p.Phe101fs (c.303del) is classified Pathogenic in OTC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-03). No gnomAD frequency available for this variant; Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.Phe101fs (c.303del)?

OTC p.Phe101fs (c.303del) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How common is OTC p.Phe101fs (c.303del) in the general population?

OTC p.Phe101fs (c.303del) 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.Phe101fs

c.303del · rs1400669703 · VCV1428221

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.67	GERP -4.6, phastCons 0.015

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

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.Phe101fs
Coding: c.303del
MANE Select: NM_000531
dbSNP: rs1400669703
Type: Deletion
Location: chrX:38381344 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 101: an α-helix; a UniProt-annotated variant site (in)

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.Phe101= Likely benign ★ 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
OTC p.Gln282fs 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-phe101fs (accessed [today's date]).

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