Is BRCA1 c.593+4del pathogenic?

BRCA1 c.593+4del is classified Conflicting classifications of pathogenicity in BRCA1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-08). Absent from gnomAD; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 c.593+4del?

BRCA1 c.593+4del is associated with hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1, pancreatic cancer, susceptibility to, 4 (ClinVar).

How common is BRCA1 c.593+4del in the general population?

BRCA1 c.593+4del is absent from gnomAD (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

BRCA1 c.593+4del

rs1555594036 · VCV531202

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +4	donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Non-coding constraint	Z 2.23	1 kb window · o/e 0.80 · regional · uncalibrated

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA1
Coding: c.593+4del
MANE Select: NM_007294
dbSNP: rs1555594036
Type: Deletion
Location: chr17:43097240 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: breast-ovarian cancer, familial, susceptibility to, 1 pancreatic cancer, susceptibility to, 4 hereditary neoplastic syndrome Fanconi anemia, complementation group S

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 c.302-2del Pathogenic ★★★ same condition
BRCA1 c.4358_4484del Pathogenic ★★★ same condition
BRCA1 c.442-22_442-13del Pathogenic ★★★ same condition
BRCA1 c.4484+1del Pathogenic ★★★ same condition
BRCA1 c.5277+1_5277+6del Pathogenic ★★★ same condition
BRCA1 c.5278-2del Pathogenic ★★★ same condition
BRCA1 c.5333-36_5406+400del Pathogenic ★★★ same condition
BRCA1 c.5470_5477del Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brca1-c-593-plus-4del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown