VCV000559799.13 - ClinVar

NM_000046.5(ARSB):c.589C>T (p.Arg197Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (6)

6 out of 6 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000046.5(ARSB):c.589C>T (p.Arg197Ter)

Variation ID: 559799 Accession: VCV000559799.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q14.1 5: 78964517 (GRCh38) [ NCBI UCSC ] 5: 78260340 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Aug 24, 2018	Apr 4, 2026	Oct 16, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000046.5:c.589C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000037.2:p.Arg197Ter	nonsense
NM_198709.3:c.589C>T	NP_942002.1:p.Arg197Ter	nonsense
NC_000005.10:g.78964517G>A
NC_000005.9:g.78260340G>A
NG_007089.1:g.27018C>T

... more HGVS ... less HGVS

Protein change

R197*

Other names

Canonical SPDI

NC_000005.10:78964516:G:A

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA360193287 dbSNP: rs773460207 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ARSB		-	-	GRCh38 GRCh37	791	1069

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Mucopolysaccharidosis type 6	Pathogenic (6)	criteria provided, multiple submitters, no conflicts	Oct 16, 2025	RCV000677579.13

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 01, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Mucopolysaccharidosis type 6	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova Accession: SCV000803095.1 First in ClinVar: Aug 24, 2018 Last updated: Aug 24, 2018 Comment: Incorrectly reported Petry (2005) J Inherit Metab Dis 28, 1027 and Karageorgos (2007) Hum Mutat 28, 897 as c.592C>T	Publications: PubMed (4) PubMed: 16435196‚ 16949067‚ 17458871‚ 30118150 Comment: show Nonsense variant (PVS1); In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Absent from GnomAD (PM2) (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: yes Observation 1 Collection method: curation Allele origin: germline Affected status: yes

Pathogenic (Apr 08, 2020) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Mucopolysaccharidosis type 6	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001338635.1 First in ClinVar: Jun 18, 2020 Last updated: Jun 18, 2020	Publications: PubMed (4) PubMed: 16435196‚ 16949067‚ 17458871‚ 30118150 Comment: show Variant summary: ARSB c.589C>T (p.Arg197X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251310 control chromosomes. c.589C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome; Examples- Petry_2005, Dou_2006, Karageorgos_2007). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal ARSB enzymatic activity (examples- Dou_2006, Karageorgos_2007). One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Apr 13, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Mucopolysaccharidosis type 6	Baylor Genetics Accession: SCV004209881.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Jun 12, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Mucopolysaccharidosis type 6	Fulgent Genetics, Fulgent Genetics Accession: SCV005673115.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jan 25, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Mucopolysaccharidosis type 6	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002236915.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 15, 2026	Publications: PubMed (3) PubMed: 16435196‚ 17458871‚ 22133300 Comment: show This sequence change creates a premature translational stop signal (p.Arg197*) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 16435196). ClinVar contains an entry for this variant (Variation ID: 559799). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Oct 16, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	Mucopolysaccharidosis type VI	Natera, Inc. Accession: SCV007533144.1 First in ClinVar: Apr 04, 2026 Last updated: Apr 04, 2026	Publications: PubMed (2) PubMed: 16949067‚ 17458871 Comment: show The c.589C>T variant in ARSB is a nonsense variant predicted to introduce a stop codon at amino acid 197. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 17458871). Functional studies show that this variant may disrupt protein function (PMID: 16949067). Given the available evidence, this variant is classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

Variant summary: ARSB c.589C>T (p.Arg197X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251310 control chromosomes. c.589C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome; Examples- Petry_2005, Dou_2006, Karageorgos_2007). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal ARSB enzymatic activity (examples- Dou_2006, Karageorgos_2007). One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

This sequence change creates a premature translational stop signal (p.Arg197*) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type VI (PMID: 16435196). ClinVar contains an entry for this variant (Variation ID: 559799). For these reasons, this variant has been classified as Pathogenic.

Comment:

The c.589C>T variant in ARSB is a nonsense variant predicted to introduce a stop codon at amino acid 197. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 17458871). Functional studies show that this variant may disrupt protein function (PMID: 16949067). Given the available evidence, this variant is classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in the ARSB gene.	Tomanin R	Human mutation	2018	PMID: 30118150
Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia.	Jurecka A	Molecular genetics and metabolism	2012	PMID: 22133300
Mutational analysis of 105 mucopolysaccharidosis type VI patients.	Karageorgos L	Human mutation	2007	PMID: 17458871
Two novel mutations of the arylsulfatase B gene in a Chinese MPS VI child undergoing bone marrow transplantation therapy.	Dou W	Clinica chimica acta; international journal of clinical chemistry	2006	PMID: 16949067
Mucopolysaccharidosis type VI: Identification of novel mutations on the arylsulphatase B gene in South American patients.	Petry MF	Journal of inherited metabolic disease	2005	PMID: 16435196

Text-mined citations for rs773460207 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026