NM_000487.6(ARSA):c.1232C>T (p.Thr411Ile) AND Metachromatic leukodystrophy

Clinical significance:Likely pathogenic (Last evaluated: Nov 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000487.6(ARSA):c.1232C>T (p.Thr411Ile)]

NM_000487.6(ARSA):c.1232C>T (p.Thr411Ile)

ARSA:arylsulfatase A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000487.6(ARSA):c.1232C>T (p.Thr411Ile)
Other names:
  • NC_000022.11:g.50625443G>A
  • NG_009260.2:g.7737C>T
  • NM_000487.6:c.1232C>TMANE SELECT
  • NM_001085425.3:c.1232C>T
  • NM_001085426.3:c.1232C>T
  • NM_001085427.3:c.1232C>T
  • NM_001085428.3:c.974C>T
  • NM_001362782.2:c.974C>T
  • NP_000478.3:p.Thr411Ile
  • NP_001078894.2:p.Thr411Ile
  • NP_001078895.2:p.Thr411Ile
  • NP_001078896.2:p.Thr411Ile
  • NP_001078897.1:p.Thr325Ile
  • NP_001349711.1:p.Thr325Ile
  • NC_000022.10:g.51063871G>A
  • NM_000487.4:c.1226C>T
NCBI staff reviewed the sequence information reported in PubMed 7909527 to determine the location of this allele on current reference sequence.
Protein change:
T325I; THR409ILE
OMIM: 607574.0039; dbSNP: rs74315481
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000487.6:c.1232C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085425.3:c.1232C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085426.3:c.1232C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085427.3:c.1232C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085428.3:c.974C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362782.2:c.974C>T - missense variant - [Sequence Ontology: SO:0001583]


Metachromatic leukodystrophy (MLD)
Metachromatic leukoencephalopathy; Sulfatide lipidosis; Cerebral sclerosis diffuse metachromatic form; See all synonyms [MedGen]
MONDO: MONDO:0018868; MedGen: C0023522; Orphanet: 512; OMIM: 250100

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000040688GeneReviewsno assertion criteria providedpathologic
(Aug 25, 2011)
not providedcuration

SCV001193858Myriad Women's Health, Inc.criteria provided, single submitter
Likely pathogenic
(Nov 12, 2019)
unknownclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providednot providednot providednot providednot providednot providednot providednot providedcuration
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing



A novel mutation in the arylsulfatase A gene associated with adult-onset metachromatic leukodystrophy without clinical evidence of neuropathy.

Suzuki C, Watanabe M, Tomiyama M, Sugimoto K, Nanba E, Jackson M, Kimura T, Seino Y, Wakasaya Y, Kawarabayashi T, Miki Y, Yamamoto-Watanabe Y, Shoji M.

Eur Neurol. 2008;60(6):310-1. doi: 10.1159/000159928. Epub 2008 Oct 3. No abstract available.

PubMed [citation]

Diffusion and ADC-map images detect ongoing demyelination on subcortical white matter in an adult metachromatic leukodystrophy patient with autoimmune Hashimoto thyroiditis.

Miura A, Kumabe Y, Kimura E, Yamashita S, Ueda A, Hirano T, Uchino M.

BMJ Case Rep. 2010 Dec 1;2010. doi:pii: bcr0120102631. 10.1136/bcr.01.2010.2631.

PubMed [citation]
See all PubMed Citations (6)

Details of each submission

From GeneReviews, SCV000040688.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided


Converted during submission to Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

From Myriad Women's Health, Inc., SCV001193858.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)


NM_000487.5(ARSA):c.1232C>T(T411I) is classified as likely pathogenic in the context of metachromatic leukodystrophy. Sources cited for classification include the following: PMID 18832844, 22798296, 21265945, 19154224, 10459747 and 7909527. Classification of NM_000487.5(ARSA):c.1232C>T(T411I) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

Support Center