This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ClinVar Genomic variation as it relates to human health
NM_001182.5(ALDH7A1):c.373A>G (p.Ile125Val)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Benign/Likely benign
9 out of 9 submissions contributed to this classification
Help
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.
9
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001182.5(ALDH7A1):c.373A>G (p.Ile125Val)
Variation ID: 128348 Accession: VCV000128348.31
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 5q23.2 5: 126583952 (GRCh38) [ NCBI UCSC ] 5: 125919644 (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 6, 2014 Apr 13, 2025 Feb 2, 2025 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001182.5:c.373A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001173.2:p.Ile125Val missense NM_001201377.2:c.289A>G NP_001188306.1:p.Ile97Val missense NM_001202404.2:c.373A>G NP_001189333.2:p.Ile125Val missense NC_000005.10:g.126583952T>C NC_000005.9:g.125919644T>C NG_008600.2:g.16439A>G - Protein change
- I125V, I97V
- Other names
-
p.I125V:ATC>GTC
- Canonical SPDI
- NC_000005.10:126583951:T:C
-
Global minor allele
frequency (GMAF) HelpThe 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.
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0.00599 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
The Genome Aggregation Database (gnomAD) 0.00144
Trans-Omics for Precision Medicine (TOPMed) 0.00268
Exome Aggregation Consortium (ExAC) 0.00307
The Genome Aggregation Database (gnomAD) 0.00178
The Genome Aggregation Database (gnomAD), exomes 0.00367
1000 Genomes Project 0.00599
1000 Genomes Project 30x 0.00562
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| ALDH7A1 | - | - |
GRCh38 GRCh37 |
1157 | 1201 | |
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. |
|---|---|---|---|---|
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jul 30, 2024 | RCV000116312.25 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 2, 2025 | RCV000204650.30 | |
| Benign (1) |
criteria provided, single submitter
|
Sep 1, 2016 | RCV002316291.9 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Jun 06, 2012)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not specified |
GeneDx
Accession: SCV000166952.12
First in ClinVar: Jun 23, 2014 Last updated: Aug 07, 2015 |
Comment:
show
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (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
|
|
|
Benign
(Sep 01, 2016)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Inborn genetic diseases |
Ambry Genetics
Accession: SCV000849759.4
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
show
This alteration is classified as 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
|
|
|
benign
(Jul 30, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not specified |
Athena Diagnostics
Accession: SCV000612313.4
First in ClinVar: Aug 07, 2015 Last updated: Jan 19, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Benign
(Jan 13, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Pyridoxine-dependent epilepsy |
Illumina Laboratory Services, Illumina
Accession: SCV000452313.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
show
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (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
(Nov 19, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not specified |
Genetic Services Laboratory, University of Chicago
Accession: SCV000150230.3
First in ClinVar: May 17, 2014 Last updated: Jun 12, 2020 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
|
|
|
Likely benign
(Apr 04, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Pyridoxine-dependent epilepsy |
Fulgent Genetics, Fulgent Genetics
Accession: SCV002797222.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Benign
(Apr 11, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Pyridoxine-dependent epilepsy |
Genome-Nilou Lab
Accession: SCV004049849.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
|
|
|
Benign
(Feb 02, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Pyridoxine-dependent epilepsy |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000260348.12
First in ClinVar: Jan 31, 2016 Last updated: Feb 25, 2025 |
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 15, 2015)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not specified |
Eurofins Ntd Llc (ga)
Accession: SCV000230160.6
First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Number of individuals with the variant: 1
Zygosity: Single Heterozygote
Sex: mixed
|
|
Comment:
Comment:
This alteration is classified as 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.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ALDH7A1 | - | - | - | - |
Text-mined citations for rs117295656 ...
HelpThese 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 May 17, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.