BRIP1 E458X (c.1372G>T, rs587780228)

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Variant

BRIP1 E458X

NM_032043.3(BRIP1):c.1372G>T (p.Glu458Ter)

Also known as

p.E458*:GAA>TAA
p.Glu458Ter
p.E458*
rs587780228

ClinVar classification: Pathogenic
Review status: 2 stars out of 4criteria provided, multiple submitters, no conflicts
Last evaluated: 24 January 2026

Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.19-9814e911Facts last changed 19 October 2026

This page as data

Add .json to the page's address, or ask for application/json, to read it as JSON.

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url <- "https://dantelabs.com/genes/brip1/variants/e458x.json"
page <- fromJSON(url)
page$variant$name

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Summary

E458X is a nonsense variant in BRIP1: it creates an early stop signal, so the protein the gene encodes is predicted to be cut short. ClinVar classifies it as pathogenic for Fanconi anemia complementation group J (criteria provided, multiple submitters, no conflicts). ClinVar also lists it under 1 more condition.

ClinVar classifications

Condition	Classification	Review status	Submissions	Last evaluated
Fanconi anemia complementation group JClinVar VCV000128156 (opens in a new tab)	Pathogenic	2 stars out of 4criteria provided, multiple submitters, no conflicts	3 submissions	24 January 2026
Hereditary breast cancerClinVar VCV000128156 (opens in a new tab)	Pathogenic	2 stars out of 4criteria provided, multiple submitters, no conflicts	5 submissions	24 January 2026

Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed.

ACMG/AMP criteria

The ACMG/AMP criteria E458X meets, from its predicted effect in BRIP1, gnomAD and ClinVar.

Criterion	Strength	Points	Rests on
PVS1Null variant where loss of function causes disease	Very strong	+8	stop_gained on NM_032043.3Expected to cause nonsense-mediated decayWhether loss of function causes disease in this gene was not checked
PP5A reputable source reports it as pathogenic	Supporting	Not counted	ClinVar: Pathogenic (criteria provided, multiple submitters, no conflicts)

On these criteria alone: +8 points, likely pathogenic.

Assessed automatically, without functional, computational or family evidence. Not a clinical classification.

Population frequency

How often E458X is seen among the people whose exomes and genomes gnomAD 4.1 brings together.

Dataset	Allele frequency	Allele count	Homozygotes	Commonest in
gnomAD exomes	0.0012%1 in 81,016	18 of 1,458,286	0	European (non-Finnish): 0.0016%
gnomAD genomes	0.0026%1 in 38,026	4 of 152,104	0	African/African American: 0.0072%

Figures from gnomAD 4.1, as gnomAD publishes them. Groups are genetic ancestry groups as gnomAD infers them. They describe the variant in gnomAD's populations, not anyone's result.

E458X in the gnomAD browser (opens in a new tab)

Molecular details

Gene	BRIP1
Transcript	NM_032043.3MANE Select
Coding DNA change (HGVS c.)	c.1372G>T
Protein change (HGVS p.)	p.Glu458Terp.E458*
Predicted consequence	Nonsense (stop gained)stop_gained (opens in a new tab)
Predicted impact	High
Position (GRCh38)	chr17:61793698 C>A
Position (GRCh37)	chr17:59871059 C>A
dbSNP ID	rs587780228 (opens in a new tab)
ClinVar Variation ID	VCV000128156 (opens in a new tab)
ClinVar Allele ID	133613
ClinGen Allele Registry ID	CA288517 (opens in a new tab)
ClinVar name	NM_032043.3(BRIP1):c.1372G>T (p.Glu458Ter)
Other names	p.E458*:GAA>TAA

BRIP1 E458X in other databases

Reports that look at this variant (3)

These Genome Test condition reports include E458X among the variants they look at.

Report	Conditions	Inheritance
DNA Repair Disease	Dna Repair Disease	Autosomal recessive
Fanconi Anemia	Fanconi Anemia	Autosomal recessive
Breast and Ovarian Cancer Genes Beyond BRCA1/2	Hereditary breast cancer	Autosomal dominant

All BRIP1 variants

Limitations

This page describes publicly available information about a genetic variant. It is not a diagnosis, and it says nothing about whether you or anyone else carries this variant.

Classifications come from ClinVar and change as new evidence is reviewed. A classification here may differ from the one in ClinVar today, or from the one a laboratory reports.

Whole genome sequencing with short reads can miss or miscall some variants, particularly in repeated or highly similar stretches of DNA and in large insertions, deletions or rearrangements.

If you have questions about a variant in your own results or in your family, talk to a genetic counsellor or your doctor.

Sources & credits

Classifications from ClinVar (release 2026-10-12), National Center for Biotechnology Information.
Condition terms from the Mondo Disease Ontology (release 2026-10-06), used under CC BY 4.0.
Gene symbols and names from the HUGO Gene Nomenclature Committee (release 2026-10-16).
Allele identifiers from the ClinGen Allele Registry (release 2026-10-19-c4908f54).
Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information.
Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-19).
Difficult regions from the Genome in a Bottle Consortium (release v3.6).
Transcripts from MANE (release v1.5), NCBI and EMBL-EBI.
Predicted consequences from mehari (release 0.11.0), with transcript models from cdot.
Built from Dante Labs data release 2026.10.19-9814e911 of 19 October 2026.

Cite this page

APA

Dante Labs. (19 October 2026). BRIP1 E458X (c.1372G>T, rs587780228) (Version 2026.10.19-9814e911). Retrieved 21 October 2026, from https://dantelabs.com/genes/brip1/variants/e458x

Vancouver

Dante Labs. BRIP1 E458X (c.1372G>T, rs587780228) [Internet]. Version 2026.10.19-9814e911. 19 October 2026 [cited 21 October 2026]. Available from: https://dantelabs.com/genes/brip1/variants/e458x

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