VCV001325070.11 - ClinVar

NM_001041.4(SI):c.4251T>G (p.Tyr1417Ter)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Pathogenic (1); Likely pathogenic (1); Uncertain significance (1)

3 out of 3 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_001041.4(SI):c.4251T>G (p.Tyr1417Ter)

Variation ID: 1325070 Accession: VCV001325070.11

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q26.1 3: 165007927 (GRCh38) [ NCBI UCSC ] 3: 164725715 (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	Nov 29, 2021	Mar 7, 2026	Nov 28, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001041.4:c.4251T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001032.2:p.Tyr1417Ter	nonsense
NC_000003.12:g.165007927A>C
NC_000003.11:g.164725715A>C
NG_017043.1:g.75569T>G

Protein change

Y1417*

Other names

Canonical SPDI

NC_000003.12:165007926:A:C

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.

Exome Aggregation Consortium (ExAC) 0.00005

The Genome Aggregation Database (gnomAD), exomes 0.00006

Trans-Omics for Precision Medicine (TOPMed) 0.00011

The Genome Aggregation Database (gnomAD) 0.00012

The Genome Aggregation Database (gnomAD) 0.00014

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

Links

ClinGen: CA2689966 dbSNP: rs142090504 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.
SI		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	1708	1730

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.
Sucrase-isomaltase deficiency	Likely pathogenic (1)	criteria provided, single submitter	Dec 21, 2023	RCV001783747.4
not provided	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Nov 28, 2025	RCV001885190.11

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.
Uncertain significance (Jul 24, 2023) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV002562614.3 First in ClinVar: Aug 23, 2022 Last updated: Jul 29, 2023	Comment: show Reported in an individuals with irritable bowel syndrome, although this variant was also present in controls (Garcia-Etxebarria et al., 2018; Zheng et al., 2021); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34186061, 32732636, 29408290, 33375084) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely pathogenic (Dec 21, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Sucrase-isomaltase deficiency	Fulgent Genetics, Fulgent Genetics Accession: SCV002810433.2 First in ClinVar: Dec 31, 2022 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 (Nov 28, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002237110.5 First in ClinVar: Mar 28, 2022 Last updated: Mar 07, 2026	Publications: PubMed (4) PubMed: 16329100‚ 23103650‚ 25452324‚ 29408290 Comment: show This sequence change creates a premature translational stop signal (p.Tyr1417*) in the SI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SI are known to be pathogenic (PMID: 16329100, 23103650, 25452324). This variant is present in population databases (rs142090504, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with irritable bowel syndrome (PMID: 29408290). ClinVar contains an entry for this variant (Variation ID: 1325070). 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

Comment:

Reported in an individuals with irritable bowel syndrome, although this variant was also present in controls (Garcia-Etxebarria et al., 2018; Zheng et al., 2021); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34186061, 32732636, 29408290, 33375084)

Comment:

This sequence change creates a premature translational stop signal (p.Tyr1417*) in the SI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SI are known to be pathogenic (PMID: 16329100, 23103650, 25452324). This variant is present in population databases (rs142090504, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with irritable bowel syndrome (PMID: 29408290). ClinVar contains an entry for this variant (Variation ID: 1325070). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients.	Garcia-Etxebarria K	Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association	2018	PMID: 29408290
Congenital sucrase-isomaltase deficiency: identification of a common Inuit founder mutation.	Marcadier JL	CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne	2015	PMID: 25452324
Four mutations in the SI gene are responsible for the majority of clinical symptoms of CSID.	Uhrich S	Journal of pediatric gastroenterology and nutrition	2012	PMID: 23103650
Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption.	Sander P	Human mutation	2006	PMID: 16329100

Text-mined citations for rs142090504 ...

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