VCV002571397.8 - ClinVar

NM_001530.4(HIF1A):c.1744C>T (p.Pro582Ser)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (1); Benign (1)

2 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_001530.4(HIF1A):c.1744C>T (p.Pro582Ser)

Variation ID: 2571397 Accession: VCV002571397.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q23.2 14: 61740839 (GRCh38) [ NCBI UCSC ] 14: 62207557 (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 17, 2023	Apr 12, 2026	Nov 24, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001530.4:c.1744C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001521.1:p.Pro582Ser	missense
NM_001243084.2:c.1816C>T	NP_001230013.1:p.Pro606Ser	missense
NM_181054.3:c.1744C>T	NP_851397.1:p.Pro582Ser	missense
NC_000014.9:g.61740839C>T
NC_000014.8:g.62207557C>T
NG_029606.1:g.50439C>T

... more HGVS ... less HGVS

Protein change

P582S, P606S

Other names

p.Pro582Ser

Canonical SPDI

NC_000014.9:61740838: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.

0.07308 (T)

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

1000 Genomes Project 30x 0.07167

1000 Genomes Project 0.07308

The Genome Aggregation Database (gnomAD) 0.07749

Trans-Omics for Precision Medicine (TOPMed) 0.08062

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.08765

Exome Aggregation Consortium (ExAC) 0.08966

The Genome Aggregation Database (gnomAD), exomes 0.09690

Links

ClinGen: CA7216005 dbSNP: rs11549465 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.
HIF1A		-	-	GRCh38 GRCh37	3	160
HIF1A-AS3	-	-	-	GRCh38	-	141

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.
Cholangiocarcinoma	other (1)	no assertion criteria provided	Dec 10, 2022	RCV003312797.3
not provided	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Nov 24, 2025	RCV003481485.6
Triple-negative breast cancer	association (1)	no assertion criteria provided	Mar 26, 2026	RCV006646202.1

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.
Uncertain significance (Nov 24, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV004226522.2 First in ClinVar: Jan 06, 2024 Last updated: Jan 11, 2026	Publications: PubMed (3) PubMed: 12919954‚ 22647679‚ 24120591 Comment: show BP4 (less) 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: 61

Benign (Jun 10, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV004562986.3 First in ClinVar: Feb 20, 2024 Last updated: Jan 24, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

other No association with disease-free or overall survival (Dec 10, 2022) N Not contributing to aggregate classification	no assertion criteria provided	Cholangiocarcinoma	Department of Surgery, Campus Charité Mitte \| Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin Accession: SCV004011744.2 First in ClinVar: Jul 16, 2023 Last updated: Apr 13, 2025	Publications: PubMed (1) PubMed: 18550579 Comment: show No association with disease-free or overall survival after resection of intrahepatic Cholangiocarcinoma (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: Central Europe

association (Mar 26, 2026) N Not contributing to aggregate classification	no assertion criteria provided	Triple-negative breast cancer	Hdge Lab, Department of Biotechnology, Mizoram University Accession: SCV007538987.1 First in ClinVar: Apr 12, 2026 Last updated: Apr 12, 2026	Comment: show Variant identified in a case-control study of breast cancer. Allele frequencies were compared between cases and controls. Significant association observed (BC: OR=1.692, 95% CI=0.135–21.270). Classified as "association" based on limited evidence. (less) Observation: 1 Collection method: case-control Allele origin: germline Affected status: yes more Observation 1 Collection method: case-control Allele origin: germline Affected status: yes Number of individuals with the variant: 2 Age: 40-70 years Sex: female Ethnicity/Population group: South Asian Geographic origin: India

Comment:

Variant identified in a case-control study of breast cancer. Allele frequencies were compared between cases and controls. Significant association observed (BC: OR=1.692, 95% CI=0.135–21.270). Classified as "association" based on limited evidence.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Hypoxia-inducible factor-1α(Pro-582-Ser) polymorphism prevents iron deprivation in healthy blood donors.	Torti L	Blood transfusion = Trasfusione del sangue	2013	PMID: 24120591
HIF1A C1772T polymorphism leads to HIF-1α mRNA overexpression in prostate cancer patients.	Vainrib M	Cancer biology & therapy	2012	PMID: 22647679
Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer.	Lurje G	Annals of oncology : official journal of the European Society for Medical Oncology	2008	PMID: 18550579
Hypoxia-inducible factor-1alpha polymorphisms associated with enhanced transactivation capacity, implying clinical significance.	Tanimoto K	Carcinogenesis	2003	PMID: 12919954

Text-mined citations for rs11549465 ...

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