Is OTC p.Phe324fs (c.970_979del) pathogenic?

OTC p.Phe324fs (c.970979del) is classified Likely pathogenic in OTC (ClinVar, No assertion criteria, 1 submitter). No gnomAD frequency available for this variant; Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.Phe324fs (c.970_979del)?

OTC p.Phe324fs (c.970_979del) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How common is OTC p.Phe324fs (c.970_979del) in the general population?

OTC p.Phe324fs (c.970_979del) 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.Phe324fs

c.970_979del · rs2147346607 · VCV1256051

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (9 of 10, 36 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1

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.Phe324fs
Coding: c.970_979del
MANE Select: NM_000531
dbSNP: rs2147346607
Type: Deletion
Location: chrX:38411963 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 324: an α-helix

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.Phe324Ser Uncertain significance ★ ⚠ same residue
OTC p.Phe324= 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

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-phe324fs (accessed [today's date]).

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