VCV000300536.22 - ClinVar

NM_002778.4(PSAP):c.88G>T (p.Ala30Ser)

Germline

Classification

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

Conflicting classifications of pathogenicity
Uncertain significance (1); Benign (1); Likely benign (5)

7 out of 7 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_002778.4(PSAP):c.88G>T (p.Ala30Ser)

Variation ID: 300536 Accession: VCV000300536.22

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q22.1 10: 71834458 (GRCh38) [ NCBI UCSC ] 10: 73594215 (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	Dec 6, 2016	Jun 20, 2026	Jan 28, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_002778.4:c.88G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002769.1:p.Ala30Ser	missense
NM_001042465.3:c.88G>T	NP_001035930.1:p.Ala30Ser	missense
NM_001042466.3:c.88G>T	NP_001035931.1:p.Ala30Ser	missense
NC_000010.11:g.71834458C>A
NC_000010.10:g.73594215C>A
NG_009301.1:g.21868G>T

... more HGVS ... less HGVS

Protein change

A30S

Other names

Canonical SPDI

NC_000010.11:71834457:C: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.

The Genome Aggregation Database (gnomAD) 0.00050

The Genome Aggregation Database (gnomAD) 0.00051

The Genome Aggregation Database (gnomAD), exomes 0.00053

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00062

Trans-Omics for Precision Medicine (TOPMed) 0.00063

Exome Aggregation Consortium (ExAC) 0.00066

The Genome Aggregation Database (gnomAD), exomes 0.00081

Links

ClinGen: CA5547906 dbSNP: rs144942998 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.
PSAP		-	-	GRCh38 GRCh37	1005	1031

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.
Combined PSAP deficiency	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000304205.5
Krabbe disease due to saposin A deficiency	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000345088.5
Gaucher disease due to saposin C deficiency	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000393668.5
Sphingolipid activator protein 1 deficiency	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 28, 2026	RCV000972285.15
not provided	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Apr 1, 2025	RCV001552293.7

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 (Aug 18, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001772957.1 First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021	Comment: show In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30037697) (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 benign (Apr 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV005909868.5 First in ClinVar: Apr 20, 2025 Last updated: Jun 20, 2026	Comment: show PSAP: BP4 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Gaucher disease due to saposin C deficiency	Illumina Laboratory Services, Illumina Accession: SCV000364181.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (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

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Krabbe disease due to saposin A deficiency	Illumina Laboratory Services, Illumina Accession: SCV000364180.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (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

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Sphingolipid activator protein 1 deficiency	Illumina Laboratory Services, Illumina Accession: SCV000364182.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (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

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Combined PSAP deficiency	Illumina Laboratory Services, Illumina Accession: SCV000364179.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (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

Benign (Jan 28, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Sphingolipid activator protein 1 deficiency	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001119988.8 First in ClinVar: Dec 17, 2019 Last updated: Mar 07, 2026	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:

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30037697)

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

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 rs144942998 ...

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 Jun 20, 2026