Is NAGS p.Phe472fs (c.1414_1415del) pathogenic?

NAGS p.Phe472fs (c.14141415del) is classified Likely pathogenic in NAGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-06). No gnomAD frequency available for this variant; Associated with hyperammonemia due to N-acetylglutamate synthase deficiency.

What condition is associated with NAGS p.Phe472fs (c.1414_1415del)?

NAGS p.Phe472fs (c.1414_1415del) is associated with hyperammonemia due to N-acetylglutamate synthase deficiency (ClinVar).

How common is NAGS p.Phe472fs (c.1414_1415del) in the general population?

NAGS p.Phe472fs (c.1414_1415del) is no gnomAD frequency available for this variant (gnomAD).

NAGS p.Phe472fs

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.1414_1415del · rs2143991359 · VCV1066206

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (6 of 7, 39 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Phe472fs
Coding: c.1414_1415del
MANE Select: NM_153006
dbSNP: rs2143991359
Type: Deletion
Location: chr17:44007734 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.38 · 1 PDB
Residue 472: a β-strand; the n-acetyltransferase domain

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 p.Phe472= Likely benign ★ same residue
NAGS c.915+2_915+6del Likely pathogenic ★★ same condition
NAGS p.Ala16fs Pathogenic/Likely pathogenic ★★ same condition
NAGS p.Arg342fs Pathogenic ★★ same condition
NAGS p.Arg465fs Likely pathogenic ★★ same condition
NAGS p.Gly24fs Pathogenic/Likely pathogenic ★★ same condition
NAGS p.Gly438fs Pathogenic ★★ same condition
NAGS p.Leu370fs Pathogenic/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-phe472fs (accessed [today's date]).

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