Is ARG1 p.Pro320fs (c.959_962del) pathogenic?

ARG1 p.Pro320fs (c.959962del) is classified Uncertain significance in ARG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-12-21). Very rare (popmax 8.47e-05%, nfe); Associated with arginase deficiency.

What condition is associated with ARG1 p.Pro320fs (c.959_962del)?

ARG1 p.Pro320fs (c.959_962del) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Pro320fs (c.959_962del) in the general population?

ARG1 p.Pro320fs (c.959_962del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Argininemia inherited?

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

ARG1 p.Pro320fs

c.959_962del · rs1554251368 · VCV555762

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

arginase deficiency

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 1.1, phastCons 0.003

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,970 alleles

Overall 0.000248% 4/1,614,076 alleles · very rare exomes 4/1,461,790 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)grpmax	8.47e-05%	1,179,970

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARG1
Protein: p.Pro320fs
Coding: c.959_962del
MANE Select: NM_000045
dbSNP: rs1554251368
Type: Deletion
Location: chr6:131583895 (GRCh38)

Full ARG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arginase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Argininemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Finland)

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/arg1-p-pro320fs (accessed [today's date]).

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