Is OTC p.Val315= (c.945C>A) pathogenic?

OTC p.Val315= (c.945C>A) is classified Likely benign in OTC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-24). Very rare (popmax 0.0035%, afr); Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.Val315= (c.945C>A)?

OTC p.Val315= (c.945C>A) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How common is OTC p.Val315= (c.945C>A) in the general population?

OTC p.Val315= (c.945C>A) is very rare (popmax 0.0035%, afr) (gnomAD).

How is Ornithine transcarbamylase deficiency inherited?

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

OTC p.Val315=

c.945C>A · rs1296441032 · VCV1149838

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0035%, afr)

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 -0.4	GERP -2.5, phastCons 0.004
Overall
CADD	1.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0035% African / African-American · 2/57,156 alleles

Filtering AF 0.00058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000249% 3/1,207,050 alleles · very rare exomes 2/1,094,975 · genomes 1/112,075 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0035%	28,578
South Asian	0.00176%	56,772

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.Val315=
Coding: c.945C>A
MANE Select: NM_000531
dbSNP: rs1296441032
Type: single nucleotide variant
Location: chrX:38411939 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 315: 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.Val315Asp Pathogenic ★★ same residue
OTC p.Val315Gly Pathogenic ★ same residue
OTC p.Val315Ile Likely pathogenic ★ ⚠ same residue
OTC p.Val315Leu Likely pathogenic ★ same residue
OTC p.Val315Phe Likely pathogenic ★ same residue
OTC p.Val315Ala Pathogenic ⚠ same residue
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-val315 (accessed [today's date]).

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