VCV000430422.13 - ClinVar

NM_002294.3(LAMP2):c.515T>C (p.Leu172Pro)

Germline

Classification

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

Conflicting classifications of pathogenicity
Uncertain significance (2); Likely benign (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_002294.3(LAMP2):c.515T>C (p.Leu172Pro)

Variation ID: 430422 Accession: VCV000430422.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq24 X: 120449011 (GRCh38) [ NCBI UCSC ] X: 119582866 (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	Jul 2, 2017	Jul 19, 2026	Jun 12, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.515T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Leu172Pro	missense
NM_001122606.1:c.515T>C	NP_001116078.1:p.Leu172Pro	missense
NM_013995.2:c.515T>C	NP_054701.1:p.Leu172Pro	missense
NC_000023.11:g.120449011A>G
NC_000023.10:g.119582866A>G
NG_007995.1:g.25339T>C
LRG_749:g.25339T>C
LRG_749t1:c.515T>C	LRG_749p1:p.Leu172Pro
LRG_749t2:c.515T>C	LRG_749p2:p.Leu172Pro
LRG_749t3:c.515T>C	LRG_749p3:p.Leu172Pro

... more HGVS ... less HGVS

Protein change

L172P

Other names

Canonical SPDI

NC_000023.11:120449010:A:G

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), exomes 0.00001

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00009

Exome Aggregation Consortium (ExAC) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00010

The Genome Aggregation Database (gnomAD) 0.00007

The Genome Aggregation Database (gnomAD) 0.00002

Links

ClinGen: CA10505296 dbSNP: rs371174243 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.
LAMP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	955	1133

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.
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	Jun 12, 2026	RCV002341168.3
not provided	Uncertain significance (1)	criteria provided, single submitter	May 19, 2017	RCV000493367.1
Danon disease	Uncertain significance (1)	criteria provided, single submitter	Feb 3, 2026	RCV001071530.9

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 (May 19, 2017) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not provided	GeneDx Accession: SCV000583220.3 First in ClinVar: Jul 02, 2017 Last updated: Jul 02, 2017	Comment: show The L172P variant of uncertain significance in the LAMP2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L172P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function. Nevertheless, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. (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

Uncertain significance (Feb 03, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001236838.7 First in ClinVar: Apr 15, 2020 Last updated: Feb 15, 2026	Comment: show This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 172 of the LAMP2 protein (p.Leu172Pro). This variant is present in population databases (rs371174243, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 430422). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LAMP2 protein function with a negative predictive value of 80%. 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. (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 (Jun 12, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002644886.3 First in ClinVar: Nov 29, 2022 Last updated: Jul 19, 2026	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (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:

The L172P variant of uncertain significance in the LAMP2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L172P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function. Nevertheless, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.

Comment:

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 172 of the LAMP2 protein (p.Leu172Pro). This variant is present in population databases (rs371174243, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 430422). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LAMP2 protein function with a negative predictive value of 80%. 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.

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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 rs371174243 ...

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 Jul 27, 2026