Is OTC p.Val130= (c.390A>G) pathogenic?

OTC p.Val130= (c.390A>G) is classified Likely benign in OTC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-20). Ultra-rare (popmax 0.0216%, nfe); Associated with ornithine carbamoyltransferase deficiency.

What condition is associated with OTC p.Val130= (c.390A>G)?

OTC p.Val130= (c.390A>G) is associated with ornithine carbamoyltransferase deficiency (ClinVar).

How common is OTC p.Val130= (c.390A>G) in the general population?

OTC p.Val130= (c.390A>G) is ultra-rare (popmax 0.0216%, 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.Val130=

c.390A>G · rs149795059 · VCV733561

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0216%, nfe)

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 0.63	GERP -4.8, phastCons 0.98
Overall
CADD	5.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0216% European (non-Finnish) · 191/885,860 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.0169% 203/1,199,465 alleles · ultra-rare exomes 187/1,087,738 · genomes 16/111,727 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0216%	4,638
Remaining individualsnot grpmax-eligible	0.0127%	7,874
South Asian	0.00531%	18,832
African / African-American	0.00527%	18,993

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.Val130=
Coding: c.390A>G
MANE Select: NM_000531
dbSNP: rs149795059
Type: single nucleotide variant
Location: chrX:38401278 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 130: 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 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
OTC c.663+2T>C 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-val130 (accessed [today's date]).

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