Is NAGS p.Pro17= (c.51G>A) pathogenic?

NAGS p.Pro17= (c.51G>A) is classified Likely benign in NAGS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). Ultra-rare (popmax 0.0194%, mid); Associated with hyperammonemia due to N-acetylglutamate synthase deficiency.

What condition is associated with NAGS p.Pro17= (c.51G>A)?

NAGS p.Pro17= (c.51G>A) is associated with hyperammonemia due to N-acetylglutamate synthase deficiency (ClinVar).

How common is NAGS p.Pro17= (c.51G>A) in the general population?

NAGS p.Pro17= (c.51G>A) is ultra-rare (popmax 0.0194%, mid) (gnomAD).

NAGS p.Pro17=

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.51G>A · rs1009436443 · VCV1562810

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, mid)

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 -0.01	GERP -2
Overall
CADD	7.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0194% Middle Eastern · 1/5,144 alleles

Filtering AF 0.00279% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.00286% 43/1,503,550 alleles · ultra-rare exomes 41/1,351,332 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0194%	5,144
European (non-Finnish)	0.00373%	26,787

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: NAGS
Protein: p.Pro17=
Coding: c.51G>A
MANE Select: NM_153006
dbSNP: rs1009436443
Type: single nucleotide variant
Location: chr17:44004714 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.38 · 1 PDB

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-pro17 (accessed [today's date]).

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