VCV000318826.9 - ClinVar

NM_001243177.4(ALDOA):c.226C>T (p.Arg76Cys)

Germline

Classification

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

Uncertain significance
Uncertain significance (4)

4 out of 4 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_001243177.4(ALDOA):c.226C>T (p.Arg76Cys)

Variation ID: 318826 Accession: VCV000318826.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p11.2 16: 30067318 (GRCh38) [ NCBI UCSC ] 16: 30078639 (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	Sep 6, 2025	Dec 21, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001243177.4:c.226C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001230106.1:p.Arg76Cys	missense
NM_001365304.2:c.*573C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_001127617.2:c.64C>T	NP_001121089.1:p.Arg22Cys	missense
NM_001365305.2:c.*573C>T		3 prime UTR
NM_001365307.2:c.*573C>T		3 prime UTR
NM_184041.4:c.64C>T
NM_184041.5:c.64C>T	NP_908930.1:p.Arg22Cys	missense
NM_184043.2:c.64C>T	NP_908932.1:p.Arg22Cys	missense
NC_000016.10:g.30067318C>T
NC_000016.9:g.30078639C>T
NG_008010.1:g.19149C>T
LRG_1180:g.19149C>T
LRG_1180t1:c.64C>T	LRG_1180p1:p.Arg22Cys
LRG_1180t2:c.226C>T	LRG_1180p2:p.Arg76Cys

... more HGVS ... less HGVS

Protein change

R22C, R76C

Other names

p.Arg22Cys

Canonical SPDI

NC_000016.10:30067317: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.

0.00040 (T)

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

The Genome Aggregation Database (gnomAD) 0.00003

Trans-Omics for Precision Medicine (TOPMed) 0.00006

The Genome Aggregation Database (gnomAD) 0.00008

The Genome Aggregation Database (gnomAD), exomes 0.00008

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

The Genome Aggregation Database (gnomAD), exomes 0.00019

Exome Aggregation Consortium (ExAC) 0.00023

1000 Genomes Project 0.00040

1000 Genomes Project 30x 0.00062

Links

ClinGen: CA8000855 dbSNP: rs145582724 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.
ALDOA		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	26	681
LOC112694756	-	-	-	GRCh38	-	491

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.
HNSHA due to aldolase A deficiency	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Dec 21, 2024	RCV000315989.9
not provided	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Dec 27, 2023	RCV004696903.2

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.
Uncertain significance (Aug 22, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	HNSHA due to aldolase A deficiency	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003297553.1 First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023	Comment: show This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 22 of the ALDOA protein (p.Arg22Cys). This variant is present in population databases (rs145582724, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ALDOA-related conditions. ClinVar contains an entry for this variant (Variation ID: 318826). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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

Uncertain significance (Aug 23, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Clinical Genetics Laboratory, Skane University Hospital Lund Accession: SCV005199513.1 First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024	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 (Dec 27, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV005411287.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	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: 1

Uncertain significance (Dec 21, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	HNSHA due to aldolase A deficiency	Revvity Omics, Revvity Accession: SCV006313166.1 First in ClinVar: Sep 06, 2025 Last updated: Sep 06, 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

Comment:

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 22 of the ALDOA protein (p.Arg22Cys). This variant is present in population databases (rs145582724, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ALDOA-related conditions. ClinVar contains an entry for this variant (Variation ID: 318826). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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 rs145582724 ...

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 Aug 16, 2026