Is OTC p.His302= (c.906C>T) pathogenic?

OTC p.His302= (c.906C>T) is classified Likely benign in OTC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-17). Very rare (popmax 0.000447%, nfe); Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.His302= (c.906C>T)?

OTC p.His302= (c.906C>T) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How common is OTC p.His302= (c.906C>T) in the general population?

OTC p.His302= (c.906C>T) is very rare (popmax 0.000447%, nfe) (gnomAD).

How is Ornithine transcarbamylase deficiency inherited?

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

OTC p.His302=

c.906C>T · rs67870244 · VCV1096485

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Conditions

ornithine carbamoyltransferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	acceptor loss · deltas
Pangolin	Δ0.30	gain · loss 0.19 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 1.7	GERP 1.2, phastCons 1
Overall
CADD	12.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000447% European (non-Finnish) · 4/894,400 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000331% 4/1,209,152 alleles · very rare exomes 2/1,097,099 · genomes 2/112,053 · 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: OTC
Protein: p.His302=
Coding: c.906C>T
MANE Select: NM_000531
dbSNP: rs67870244
Type: single nucleotide variant
Location: chrX:38411900 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 302: a UniProt-annotated variant site (in otcd; female; late onset); a UniProt-annotated variant site (in otcd; late onset); a UniProt-annotated variant site (in otcd; neonatal); a β-strand

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.His302Asp Likely pathogenic ★ same residue
OTC p.His302Arg Pathogenic same residue
OTC p.His302Gln Pathogenic same residue
OTC p.His302Leu Pathogenic same residue
OTC p.His302Tyr Pathogenic same residue
OTC c.298+2T>G Pathogenic ★★ same condition
OTC c.299-1G>A Likely pathogenic ★★ same condition
OTC c.386+1G>A 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-his302 (accessed [today's date]).

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