Is OTC p.Ala102= (c.306A>T) pathogenic?

OTC p.Ala102= (c.306A>T) is classified Likely benign in OTC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). Absent from gnomAD v4.1; Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.Ala102= (c.306A>T)?

OTC p.Ala102= (c.306A>T) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How common is OTC p.Ala102= (c.306A>T) in the general population?

OTC p.Ala102= (c.306A>T) is absent from gnomAD v4.1 (gnomAD).

How is Ornithine transcarbamylase deficiency inherited?

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

OTC p.Ala102=

c.306A>T · rs2519959101 · VCV2765595

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ornithine carbamoyltransferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.048	GERP -0.16, phastCons 0.21
Overall
CADD	7.784	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OTC
Protein: p.Ala102=
Coding: c.306A>T
MANE Select: NM_000531
dbSNP: rs2519959101
Type: single nucleotide variant
Location: chrX:38381349 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 102: an α-helix; a UniProt-annotated variant site (in otcd)

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.Ala102Glu 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
OTC c.540+1G>A Pathogenic ★★ same condition
OTC c.540+1G>T Pathogenic ★★ same condition
OTC c.540+265G>A Pathogenic ★★ same condition
OTC c.663+1G>T 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-ala102 (accessed [today's date]).

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