VCV000531680.7 - ClinVar

NM_000304.4(PMP22):c.83G>A (p.Trp28Ter)

Germline

Classification

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

Pathogenic

2 out of 2 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_000304.4(PMP22):c.83G>A (p.Trp28Ter)

Variation ID: 531680 Accession: VCV000531680.7

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17p12 17: 15259189 (GRCh38) [ NCBI UCSC ] 17: 15162506 (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 28, 2018	Oct 25, 2025	Nov 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000304.4:c.83G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000295.1:p.Trp28Ter	nonsense
NM_001281455.2:c.83G>A	NP_001268384.1:p.Trp28Ter	nonsense
NM_001281456.2:c.83G>A	NP_001268385.1:p.Trp28Ter	nonsense
NM_001330143.2:c.83G>A	NP_001317072.1:p.Trp28Ter	nonsense
NM_153321.3:c.83G>A	NP_696996.1:p.Trp28Ter	nonsense
NM_153322.3:c.83G>A	NP_696997.1:p.Trp28Ter	nonsense
NR_104017.2:n.178G>A		non-coding transcript variant
NC_000017.11:g.15259189C>T
NC_000017.10:g.15162506C>T
NG_007949.1:g.11139G>A
LRG_263:g.11139G>A

... more HGVS ... less HGVS

Protein change

W28*

Other names

Canonical SPDI

NC_000017.11:15259188:C: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.

Links

ClinGen: CA398271192 dbSNP: rs1555568475 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.
PMP22		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	452	587

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.
Charcot-Marie-Tooth disease, type I	Pathogenic (1)	criteria provided, single submitter	Aug 28, 2024	RCV000638157.7
Hereditary liability to pressure palsies	Pathogenic (1)	criteria provided, single submitter	Nov 22, 2024	RCV005870719.1

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.
Pathogenic (Aug 28, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Charcot-Marie-Tooth disease, type I	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000759643.6 First in ClinVar: May 28, 2018 Last updated: Feb 25, 2025	Publications: PubMed (1) PubMed: 23224996 Comment: show This sequence change creates a premature translational stop signal (p.Trp28*) in the PMP22 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMP22 are known to be pathogenic (PMID: 23224996). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary neuropathy with liability to pressure palsies (internal data). ClinVar contains an entry for this variant (Variation ID: 531680). 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

Pathogenic (Nov 22, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary liability to pressure palsies	3billion Accession: SCV006583552.1 First in ClinVar: Oct 25, 2025 Last updated: Oct 25, 2025	Comment: show The variant is not observed in the gnomAD v4.1.0 dataset. Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with PMP22 related disorder (ClinVar ID: VCV000531680). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (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 Method: exome sequencing

Comment:

This sequence change creates a premature translational stop signal (p.Trp28*) in the PMP22 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMP22 are known to be pathogenic (PMID: 23224996). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary neuropathy with liability to pressure palsies (internal data). ClinVar contains an entry for this variant (Variation ID: 531680). For these reasons, this variant has been classified as Pathogenic.

Comment:

The variant is not observed in the gnomAD v4.1.0 dataset. Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with PMP22 related disorder (ClinVar ID: VCV000531680). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The PMP22 gene and its related diseases.	Li J	Molecular neurobiology	2013	PMID: 23224996

Text-mined citations for rs1555568475 ...

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 Oct 26, 2025