Is BRCA1 c.441+17del pathogenic?

BRCA1 c.441+17del is classified Benign/Likely benign in BRCA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-10). Rare (popmax 0.101%, afr); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 c.441+17del?

BRCA1 c.441+17del is associated with hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BRCA1 c.441+17del in the general population?

BRCA1 c.441+17del is rare (popmax 0.101%, afr) (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.441+17del

rs730881449 · VCV462647

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

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 +17	near-intronic (+17 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.17	GERP -2.4, phastCons 0.003
Non-coding constraint	Z 0.28	1 kb window · o/e 0.98 · regional · uncalibrated
Overall
CADD	0.145	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(AAG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% African / African-American · 73/72,470 alleles

Filtering AF 0.0821% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0753%

Overall 0.00506% 79/1,561,140 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	993
Remaining individualsnot grpmax-eligible	0.00659%	15,165
European (non-Finnish)	0.000175%	570,373

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRCA1
Coding: c.441+17del
MANE Select: NM_007294
dbSNP: rs730881449
Type: Deletion
Location: chr17:43104105 (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: hereditary neoplastic syndrome hereditary breast carcinoma

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.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
BRCA1 n.5274delG 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-441-plus-17del (accessed [today's date]).

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