Is ARG1 p.Arg32fs (c.93del) pathogenic?

ARG1 p.Arg32fs (c.93del) is classified Pathogenic in ARG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-11). Very rare (popmax 0.00329%, sas); Associated with arginase deficiency.

What condition is associated with ARG1 p.Arg32fs (c.93del)?

ARG1 p.Arg32fs (c.93del) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Arg32fs (c.93del) in the general population?

ARG1 p.Arg32fs (c.93del) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Argininemia inherited?

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

ARG1 p.Arg32fs

c.93del · rs755975244 · VCV1076486

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

arginase 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	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,614,084 alleles · very rare exomes 3/1,461,774 · genomes 0/152,310 · joint denominator

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.Arg32fs
Coding: c.93del
MANE Select: NM_000045
dbSNP: rs755975244
Type: Deletion
Location: chr6:131576698 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.01 · 60 PDB
Residue 32: an α-helix

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)

Similar variants

ARG1 p.Gly272fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.His228_Leu229insTer Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.Leu216fs Pathogenic ★★ same condition
ARG1 p.Lys313fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 c.131-7_131-2del Uncertain significance ★★ same condition
ARG1 c.131-8_131-2del Likely pathogenic ★ same condition
ARG1 c.306-1del Likely pathogenic ★ same condition
ARG1 c.457_465+18del 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/arg1-p-arg32fs (accessed [today's date]).

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