VCV000876576.11 - ClinVar

NM_006642.5(SDCCAG8):c.1588G>A (p.Glu530Lys)

Germline

Classification

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

Uncertain significance
Uncertain significance (4)

4 out of 5 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.1588G>A (p.Glu530Lys)

Variation ID: 876576 Accession: VCV000876576.11

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q43 1: 243378835 (GRCh38) [ NCBI UCSC ] 1: 243542137 (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	May 31, 2020	Jan 11, 2026	Oct 18, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_006642.5:c.1588G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006633.1:p.Glu530Lys	missense
NM_001350246.2:c.685G>A	NP_001337175.1:p.Glu229Lys	missense
NM_001350247.2:c.685G>A	NP_001337176.1:p.Glu229Lys	missense
NM_001350248.2:c.1684G>A	NP_001337177.1:p.Glu562Lys	missense
NM_001350249.2:c.1294G>A	NP_001337178.1:p.Glu432Lys	missense
NM_001350251.2:c.685G>A	NP_001337180.1:p.Glu229Lys	missense
NC_000001.11:g.243378835G>A
NC_000001.10:g.243542137G>A
NG_027811.1:g.127831G>A

... more HGVS ... less HGVS

Protein change

E229K, E530K, E432K, E562K

Other names

Canonical SPDI

NC_000001.11:243378834: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.

Exome Aggregation Consortium (ExAC) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00002

The Genome Aggregation Database (gnomAD) 0.00003

The Genome Aggregation Database (gnomAD) 0.00004

Links

ClinGen: CA1483683 dbSNP: rs190020173 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	754	959

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	Uncertain significance (1)	criteria provided, single submitter	Jan 13, 2018	RCV001101540.4
Senior-Loken syndrome 7	Uncertain significance (1)	criteria provided, single submitter	Jan 13, 2018	RCV001101539.4
Bardet-Biedl syndrome 16 Senior-Loken syndrome 7	Uncertain significance (1)	criteria provided, single submitter	Dec 1, 2021	RCV001856379.5
SDCCAG8-related disorder	Uncertain significance (1)	no assertion criteria provided	Jan 23, 2024	RCV004536154.2
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Oct 18, 2025	RCV006372092.1

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 (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Senior-Loken syndrome 7	Illumina Laboratory Services, Illumina Accession: SCV001258155.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (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 (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Bardet-Biedl syndrome 16	Illumina Laboratory Services, Illumina Accession: SCV001258156.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (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 (Dec 01, 2021) 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: SCV002153026.4 First in ClinVar: Mar 28, 2022 Last updated: Mar 04, 2025	Comment: show 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 876576). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is present in population databases (rs190020173, gnomAD 0.005%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 530 of the SDCCAG8 protein (p.Glu530Lys). (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 (Oct 18, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV007239748.1 First in ClinVar: Jan 11, 2026 Last updated: Jan 11, 2026	Comment: show The c.1588G>A (p.E530K) alteration is located in exon 13 (coding exon 13) of the SDCCAG8 gene. This alteration results from a G to A substitution at nucleotide position 1588, causing the glutamic acid (E) at amino acid position 530 to be replaced by a lysine (K). 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

Uncertain significance (Jan 23, 2024) N Not contributing to aggregate classification	no assertion criteria provided	SDCCAG8-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004731643.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show The SDCCAG8 c.1588G>A variant is predicted to result in the amino acid substitution p.Glu530Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (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:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 876576). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is present in population databases (rs190020173, gnomAD 0.005%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 530 of the SDCCAG8 protein (p.Glu530Lys).

Comment:

The c.1588G>A (p.E530K) alteration is located in exon 13 (coding exon 13) of the SDCCAG8 gene. This alteration results from a G to A substitution at nucleotide position 1588, causing the glutamic acid (E) at amino acid position 530 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

The SDCCAG8 c.1588G>A variant is predicted to result in the amino acid substitution p.Glu530Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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 rs190020173 ...

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