NM_000045.4(ARG1):c.703G>A (p.Gly235Arg) AND Arginase deficiency

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Nov 4, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000667889.23

Allele description [Variation Report for NM_000045.4(ARG1):c.703G>A (p.Gly235Arg)]

NM_000045.4(ARG1):c.703G>A (p.Gly235Arg)

Genes:

ARG1:arginase 1 [Gene - OMIM - HGNC]
MED23:mediator complex subunit 23 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q23.2

Genomic location:

Preferred name:

NM_000045.4(ARG1):c.703G>A (p.Gly235Arg)

HGVS:

NC_000006.12:g.131583392G>A
NG_007086.2:g.15168G>A
NG_031860.2:g.49832C>T
NM_000045.4:c.703G>AMANE SELECT
NM_001244438.2:c.727G>A
NM_001270521.2:c.4077+4317C>T
NM_001369020.1:c.448G>A
NM_015979.4:c.4095+4317C>T
NP_000036.2:p.Gly235Arg
NP_001231367.1:p.Gly243Arg
NP_001355949.1:p.Gly150Arg
NC_000006.11:g.131904532G>A
NM_000045.2:c.703G>A
NM_000045.3:c.703G>A
NR_160934.1:n.687G>A

Protein change:

G150R

Links:

dbSNP: rs104893948

Molecular consequence:

NM_001270521.2:c.4077+4317C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_015979.4:c.4095+4317C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000045.4:c.703G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001244438.2:c.727G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369020.1:c.448G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_160934.1:n.687G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Arginase deficiency
Synonyms:: ARGININEMIA; ARG1 DEFICIENCY
Identifiers:: MONDO: MONDO:0008814; MedGen: C0268548; Orphanet: 90; OMIM: 207800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000792401	Counsyl	no assertion criteria provided	Likely pathogenic (Jun 23, 2017)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11883902, 8902193, 23859858, 7649538, 27038030
SCV001389267	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 4, 2025)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 7649538, 23859858, 11883902, 28492532
SCV004200541	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 6, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005667152	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Loss of function mutations in conserved regions of the human arginase I gene.

Vockley JG, Goodman BK, Tabor DE, Kern RM, Jenkinson CP, Grody WW, Cederbaum SD.

Biochem Mol Med. 1996 Oct;59(1):44-51.

PubMed [citation]

PMID:: 8902193

Clinical phenotype, biochemical profile, and treatment in 19 patients with arginase 1 deficiency.

Huemer M, Carvalho DR, Brum JM, Ünal Ö, Coskun T, Weisfeld-Adams JD, Schrager NL, Scholl-Bürgi S, Schlune A, Donner MG, Hersberger M, Gemperle C, Riesner B, Ulmer H, Häberle J, Karall D.

J Inherit Metab Dis. 2016 May;39(3):331-340. doi: 10.1007/s10545-016-9928-y. Epub 2016 Apr 1.

PubMed [citation]

PMID:: 27038030

See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000792401.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001389267.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 235 of the ARG1 protein (p.Gly235Arg). This variant is present in population databases (rs104893948, gnomAD 0.009%). This missense change has been observed in individual(s) with arginase deficiency (PMID: 7649538, 23859858). ClinVar contains an entry for this variant (Variation ID: 419417). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ARG1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ARG1 function (PMID: 11883902). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004200541.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV005667152.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 6, 2026

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