Is ARG1 p.Arg92fs (c.272dup) pathogenic?

ARG1 p.Arg92fs (c.272dup) is classified Pathogenic in ARG1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-17). Ultra-rare (popmax 0.0174%, afr); Associated with arginase deficiency.

What condition is associated with ARG1 p.Arg92fs (c.272dup)?

ARG1 p.Arg92fs (c.272dup) is associated with arginase deficiency (ClinVar).

How common is ARG1 p.Arg92fs (c.272dup) in the general population?

ARG1 p.Arg92fs (c.272dup) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

How is Argininemia inherited?

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

ARG1 p.Arg92fs

c.272dup · rs796051923 · VCV203606

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.9	GERP -4.9
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,860 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000806% 13/1,613,808 alleles · ultra-rare exomes 5/1,461,804 · genomes 8/152,004 · 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.Arg92fs
Coding: c.272dup
MANE Select: NM_000045
dbSNP: rs796051923
Type: Duplication
Location: chr6:131579250 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.01 · 60 PDB

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.Arg92Ile Uncertain significance ★ same residue
ARG1 p.Ala125fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.Asp117fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.Asp237fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.Ile227fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 p.Phe147fs Pathogenic/Likely pathogenic ★★ same condition
ARG1 c.306-1_307dup Uncertain significance ★★ same condition
ARG1 c.802+76dup Benign ★★ 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-arg92fs (accessed [today's date]).

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