VCV000016899.15 - ClinVar

NM_000769.1(CYP2C19):c.636G>A (p.Trp212Ter)

Germline

Practice guidelines

Practice guidelines. Learn more about how ClinVar calculates review status.

Drug response

for CYP2C19: no function

Classification is based on the practice guideline submission

by Clinical Pharmacogenetics Implementation Consortium

The classification 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

This variant is part of 34 Genotypes

CYP2C19*3/*17
CYP2C19*3/*18
CYP2C19*3/*28
CYP2C19*3/*10
CYP2C19*3/*16
CYP2C19*3/*27
CYP2C19*3/*29
CYP2C19*3/*30
CYP2C19*3/*31
CYP2C19*3/*11
CYP2C19*3/*14
CYP2C19*3/*32
CYP2C19*3/*22
CYP2C19*3/*24
CYP2C19*3/*33
CYP2C19*3/*25
CYP2C19*3/*26
CYP2C19*3/*9
CYP2C19*3/*6
CYP2C19*3/*7
CYP2C19*3/*8
CYP2C19*3/*12
CYP2C19*3/*34
CYP2C19*3/*3
CYP2C19*1/*3
CYP2C19*2/*3
CYP2C19*3/*13
CYP2C19*3/*15
CYP2C19*3/*19
CYP2C19*3/*35
CYP2C19*3/*4A
CYP2C19*3/*4B
CYP2C19*3/*5
CYP2C19*3/*23

Identifiers

NM_000769.1(CYP2C19):c.636G>A (p.Trp212Ter)

Variation ID: 16899 Accession: VCV000016899.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q23.33 10: 94780653 (GRCh38) [ NCBI UCSC ] 10: 96540410 (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 22, 2016	Aug 3, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000769.4:c.636G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000760.1:p.Trp212Ter	nonsense
NM_000769.2:c.636G>A
NC_000010.11:g.94780653G>A
NC_000010.10:g.96540410G>A
NG_008384.3:g.22973G>A

... more HGVS ... less HGVS

Protein change

W212*

Other names

CYP2C19, TRP212TER (rs4986893)
CYP2C19m2
CYP2C19*3

Canonical SPDI

NC_000010.11:94780652: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.

0.01418 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00251

Trans-Omics for Precision Medicine (TOPMed) 0.00267

The Genome Aggregation Database (gnomAD), exomes 0.00538

The Genome Aggregation Database (gnomAD) 0.00149

Exome Aggregation Consortium (ExAC) 0.00551

1000 Genomes Project 30x 0.01312

1000 Genomes Project 0.01418

Links

PharmGKB Clinical Annotation: 981201917 OMIM: 124020.0003 dbSNP: rs4986893 ClinGen: CA126963 Genetic Testing Registry (GTR): GTR000501203 Genetic Testing Registry (GTR): GTR000556609 Genetic Testing Registry (GTR): GTR000569522 Genetic Testing Registry (GTR): GTR000613302 Genetic Testing Registry (GTR): GTR000613418 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.
CYP2C19		-	-	GRCh38 GRCh37	254	678

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.
MEPHENYTOIN, POOR METABOLISM OF	drug response (1)	no assertion criteria provided	Jun 1, 2009	RCV000018397.36
PROGUANIL, POOR METABOLISM OF	drug response (1)	no assertion criteria provided	Jun 1, 2009	RCV000018398.36
not provided	Benign; other (2)	criteria provided, multiple submitters, no conflicts	Aug 6, 2018	RCV000291495.15
CYP2C19: no function	drug response (1)	practice guideline	-	RCV000783656.10
Acute coronary syndrome	drug response (1)	no assertion criteria provided	-	RCV002280093.8
Clopidogrel response	drug response (1)	no assertion criteria provided	-	RCV004813044.2

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.
drug response Allele function (-) C Contributing to aggregate classification	practice guideline (Clinical Pharmacogenetics Implementation Consortium)	CYP2C19: no function	Clinical Pharmacogenetics Implementation Consortium Accession: SCV000922179.2 First in ClinVar: Jun 17, 2019 Last updated: Aug 03, 2025	Other databases https://www.pharmgkb.org/haploty… https://www.pharmgkb.org/haplotype/PA166128326 https://cpicpgx.org https://cpicpgx.org Observation: 1 Collection method: curation Allele origin: germline Affected status: not applicable more Observation 1 Collection method: curation Allele origin: germline Affected status: not applicable Comment on evidence: "No function" was previously submitted as the functional consequence for CYP2C19*3, but without providing the result of a functional assay.

Benign (Aug 06, 2018) N Not contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Not Provided	GeneDx Accession: SCV001904711.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Comment: show This variant is associated with the following publications: (PMID: 22865819, 20549256, 21855977, 22344438, 25087612, 25525159, 23874401, 7969038, 24906606) (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

other Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles). (Dec 28, 2015) N Not contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000331713.4 First in ClinVar: Dec 06, 2016 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2C19 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 5 Zygosity: 5 Single Heterozygotes Sex: mixed

drug response (Jun 01, 2009) N Not contributing to aggregate classification	no assertion criteria provided	MEPHENYTOIN, POOR METABOLISM OF	OMIM Accession: SCV000038679.2 First in ClinVar: Apr 04, 2013 Last updated: May 17, 2018	Publications: PubMed (3) PubMed: 7969038‚ 9093256‚ 19444287 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: This allelic variant is also known as CYP2C193 and CYP2C19m2. De Morais et al. (1994) identified a G-to-A mutation at nucleotide 636 in exon 4 … (more) This allelic variant is also known as CYP2C193 and CYP2C19m2. De Morais et al. (1994) identified a G-to-A mutation at nucleotide 636 in exon 4 of the CYP2C19 gene in Japanese poor metabolizers (609535). The mutation resulted in a premature termination codon (trp212 to ter; W212X). Using PCR, Kaneko et al. (1997) determined the distribution of the CYP2C192 (124020.0001) and CYP2C193 mutations in 493 individuals from 2 of the 80 islands of Vanuatu, where malaria is endemic. The CYP2C192 allele represented 698 of 986 alleles (70.6%), and the CYP2C193 allele represented 131 of 986 alleles (13.3%). Only 145 individuals had at least 1 wildtype allele. Further studies showed that homozygosity or compound heterozygosity for the mutations were associated with poor metabolism of proguanil, which is recommended for malaria chemoprophylaxis. The data suggested that 348 of the 493 individuals (70.6%) studied had the poor metabolizer phenotype, a finding with major implications for the efficacy of proguanil in this population. In a population-based study of 359 unrelated mainland Chinese, consisting of 103 Han, 107 Kazakh, and 149 Uygur individuals, Wang et al. (2009) found that the frequencies of the CYP2C19*3 allele were similar among the 3 groups (7.2%, 8.0%, and 9.4%, respectively) and higher than that reported in Caucasians (0%). (less)

drug response (Jun 01, 2009) N Not contributing to aggregate classification	no assertion criteria provided	PROGUANIL, POOR METABOLISM OF	OMIM Accession: SCV000038680.2 First in ClinVar: Apr 04, 2013 Last updated: May 17, 2018	Publications: PubMed (3) PubMed: 7969038‚ 9093256‚ 19444287 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: This allelic variant is also known as CYP2C193 and CYP2C19m2. De Morais et al. (1994) identified a G-to-A mutation at nucleotide 636 in exon 4 … (more) This allelic variant is also known as CYP2C193 and CYP2C19m2. De Morais et al. (1994) identified a G-to-A mutation at nucleotide 636 in exon 4 of the CYP2C19 gene in Japanese poor metabolizers (609535). The mutation resulted in a premature termination codon (trp212 to ter; W212X). Using PCR, Kaneko et al. (1997) determined the distribution of the CYP2C192 (124020.0001) and CYP2C193 mutations in 493 individuals from 2 of the 80 islands of Vanuatu, where malaria is endemic. The CYP2C192 allele represented 698 of 986 alleles (70.6%), and the CYP2C193 allele represented 131 of 986 alleles (13.3%). Only 145 individuals had at least 1 wildtype allele. Further studies showed that homozygosity or compound heterozygosity for the mutations were associated with poor metabolism of proguanil, which is recommended for malaria chemoprophylaxis. The data suggested that 348 of the 493 individuals (70.6%) studied had the poor metabolizer phenotype, a finding with major implications for the efficacy of proguanil in this population. In a population-based study of 359 unrelated mainland Chinese, consisting of 103 Han, 107 Kazakh, and 149 Uygur individuals, Wang et al. (2009) found that the frequencies of the CYP2C19*3 allele were similar among the 3 groups (7.2%, 8.0%, and 9.4%, respectively) and higher than that reported in Caucasians (0%). (less)

drug response (-) N Not contributing to aggregate classification	no assertion criteria provided	Acute coronary syndrome	Cardiology Department, The First Affiliated Hospital of Nanjing Medical University Accession: SCV002568452.1 First in ClinVar: Sep 03, 2022 Last updated: Sep 03, 2022	Publications: PubMed (1) PubMed: 27441996 Observation: 1 Collection method: research Allele origin: biparental Affected status: unknown more Observation 1 Collection method: research Allele origin: biparental Affected status: unknown Number of individuals with the variant: 8

drug response likely responsive (-) N Not contributing to aggregate classification	no assertion criteria provided	Clopidogrel Response Drug used for Coronary Artery Disease	Faculty of Pharmacy, Damascus University Accession: SCV005438652.2 First in ClinVar: Dec 22, 2024 Last updated: Apr 13, 2025	Comment: show rs4986893 is a SNP in the CYP2C19 gene and is linked to poor clopidogrel metabolic activation. rs4986893 is associated with reduced enzyme activity of CYP2C19 and lower concentration of clopidogrel active metabolite. (less) Observation: 1 Collection method: research Allele origin: germline Affected status: yes more Observation 1 Collection method: research Allele origin: germline Affected status: yes Sex: mixed Geographic origin: Syria

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC).	Caudle KE	Genetics in medicine : official journal of the American College of Medical Genetics	2017	PMID: 27441996
Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland Chinese Kazakh, Uygur and Han populations.	Wang SM	Journal of human genetics	2009	PMID: 19444287
High frequencies of CYP2C19 mutations and poor metabolism of proguanil in Vanuatu.	Kaneko A	Lancet (London, England)	1997	PMID: 9093256
Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese.	De Morais SM	Molecular pharmacology	1994	PMID: 7969038
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2C19	-	-	-	-
https://cpicpgx.org	-	-	-	-
https://www.pharmgkb.org/haplotype/PA166128326	-	-	-	-

Text-mined citations for rs4986893 ...

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 Jan 11, 2026