VCV001488083.13 - ClinVar

NM_006642.5(SDCCAG8):c.832C>T (p.Arg278Cys)

Germline

Classification

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

Uncertain significance

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_006642.5(SDCCAG8):c.832C>T (p.Arg278Cys)

Variation ID: 1488083 Accession: VCV001488083.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q43 1: 243308080 (GRCh38) [ NCBI UCSC ] 1: 243471382 (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	Mar 28, 2022	Feb 23, 2026	Oct 30, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_006642.5:c.832C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006633.1:p.Arg278Cys	missense
NM_001350246.2:c.-72C>T		5 prime UTR
NM_001350247.2:c.-72C>T		5 prime UTR
NM_001350248.2:c.928C>T	NP_001337177.1:p.Arg310Cys	missense
NM_001350249.2:c.538C>T	NP_001337178.1:p.Arg180Cys	missense
NM_001350251.2:c.-72C>T		5 prime UTR
NM_006642.3:c.832C>T
NC_000001.11:g.243308080C>T
NC_000001.10:g.243471382C>T
NG_027811.1:g.57076C>T

... more HGVS ... less HGVS

Protein change

R278C, R310C, R180C

Other names

Canonical SPDI

NC_000001.11:243308079:C:T

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) 0.00002

The Genome Aggregation Database (gnomAD) 0.00008

The Genome Aggregation Database (gnomAD) 0.00009

Trans-Omics for Precision Medicine (TOPMed) 0.00009

Links

ClinGen: CA1483451 dbSNP: rs769004589 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.
SDCCAG8		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh38 GRCh37	753	958

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.
Bardet-Biedl syndrome 16 Senior-Loken syndrome 7	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	May 21, 2024	RCV002033710.10
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Oct 30, 2025	RCV003303581.3

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 (Nov 22, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Bardet-Biedl syndrome 16 Senior-Loken syndrome 7 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002270107.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 23, 2026	Comment: show ClinVar contains an entry for this variant (Variation ID: 1488083). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDCCAG8 protein function. This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is present in population databases (rs769004589, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 278 of the SDCCAG8 protein (p.Arg278Cys). (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

Uncertain significance (May 21, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Senior-Loken syndrome 7 Bardet-Biedl syndrome 16 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Fulgent Genetics, Fulgent Genetics Accession: SCV002781878.2 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

Uncertain significance (Oct 30, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV003976788.3 First in ClinVar: Jul 08, 2023 Last updated: Jan 11, 2026	Comment: show The c.832C>T (p.R278C) alteration is located in exon 8 (coding exon 8) of the SDCCAG8 gene. This alteration results from a C to T substitution at nucleotide position 832, causing the arginine (R) at amino acid position 278 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (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:

ClinVar contains an entry for this variant (Variation ID: 1488083). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDCCAG8 protein function. This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is present in population databases (rs769004589, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 278 of the SDCCAG8 protein (p.Arg278Cys).

Comment:

The c.832C>T (p.R278C) alteration is located in exon 8 (coding exon 8) of the SDCCAG8 gene. This alteration results from a C to T substitution at nucleotide position 832, causing the arginine (R) at amino acid position 278 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs769004589 ...

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