VCV000305955.10 - ClinVar

NM_001360.3(DHCR7):c.1083C>A (p.Phe361Leu)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic

This classification is based on the single submission received

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_001360.3(DHCR7):c.1083C>A (p.Phe361Leu)

Variation ID: 305955 Accession: VCV000305955.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.4 11: 71435720 (GRCh38) [ NCBI UCSC ] 11: 71146766 (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	Mar 7, 2026	Sep 12, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001360.3:c.1083C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001351.2:p.Phe361Leu	missense
NM_001163817.2:c.1083C>A	NP_001157289.1:p.Phe361Leu	missense
NC_000011.10:g.71435720G>T
NC_000011.9:g.71146766G>T
NG_012655.2:g.17712C>A
LRG_340:g.17712C>A
LRG_340t1:c.1083C>A	LRG_340p1:p.Phe361Leu

... more HGVS ... less HGVS

Protein change

F361L

Other names

Canonical SPDI

NC_000011.10:71435719:G: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.

The Genome Aggregation Database (gnomAD), exomes 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

Links

ClinGen: CA6162320 dbSNP: rs780088227 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.
DHCR7		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1166	1182

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.
Smith-Lemli-Opitz syndrome	Pathogenic (1)	criteria provided, single submitter	Sep 12, 2023	RCV000292578.13

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.
Pathogenic (Sep 12, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Smith-Lemli-Opitz syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002231879.5 First in ClinVar: Mar 28, 2022 Last updated: Mar 07, 2026	Publications: PubMed (1) PubMed: 23790112 Comment: show ClinVar contains an entry for this variant (Variation ID: 305955). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 361 of the DHCR7 protein (p.Phe361Leu). This variant is present in population databases (rs780088227, gnomAD 0.002%). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 23790112). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 expected to disrupt DHCR7 protein function. 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:

ClinVar contains an entry for this variant (Variation ID: 305955). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 361 of the DHCR7 protein (p.Phe361Leu). This variant is present in population databases (rs780088227, gnomAD 0.002%). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 23790112). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 expected to disrupt DHCR7 protein function. For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Pregnancy in an individual with mild Smith-Lemli-Opitz syndrome.	Ellingson MS	Clinical genetics	2014	PMID: 23790112

Text-mined citations for rs780088227 ...

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