Is NAGS p.Pro231= (c.693C>T) pathogenic?

NAGS p.Pro231= (c.693C>T) is classified Likely benign in NAGS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). No allele count reported in gnomAD v4.1 (AN 1,549,050); Associated with hyperammonemia due to N-acetylglutamate synthase deficiency.

What condition is associated with NAGS p.Pro231= (c.693C>T)?

NAGS p.Pro231= (c.693C>T) is associated with hyperammonemia due to N-acetylglutamate synthase deficiency (ClinVar).

How common is NAGS p.Pro231= (c.693C>T) in the general population?

NAGS p.Pro231= (c.693C>T) is no allele count reported in gnomAD v4.1 (AN 1,549,050) (gnomAD).

NAGS p.Pro231=

Q: How is Hyperammonemia due to N-acetylglutamate synthase deficiency inherited?

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

c.693C>T · rs1429846887 · VCV2770724

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,549,050)

Conditions

hyperammonemia due to N-acetylglutamate synthase 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 -3	GERP -3.8
Overall
CADD	4.685	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,549,050). 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: NAGS
Protein: p.Pro231=
Coding: c.693C>T
MANE Select: NM_153006
dbSNP: rs1429846887
Type: single nucleotide variant
Location: chr17:44005903 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.38 · 1 PDB
Residue 231: the 'amino-acid kinase domain (aak)' region

Full NAGS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperammonemia due to N-acetylglutamate synthase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperammonemia due to N-acetylglutamate synthase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

NAGS c.1097-1G>C Pathogenic ★★ same condition
NAGS c.1097-2A>G Pathogenic/Likely pathogenic ★★ same condition
NAGS c.701+1G>A Likely pathogenic ★★ same condition
NAGS c.915+1G>T Likely pathogenic ★★ same condition
NAGS c.916-2A>T Pathogenic/Likely pathogenic ★★ same condition
NAGS p.Arg208Ter Pathogenic/Likely pathogenic ★★ same condition
NAGS p.Gln247Ter Pathogenic/Likely pathogenic ★★ same condition
NAGS p.Glu142Ter 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/nags-p-pro231 (accessed [today's date]).

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