Is BRCA1 c.547+14del pathogenic?

BRCA1 c.547+14del is classified Conflicting classifications of pathogenicity in BRCA1 (ClinVar, Conflicting submitters, 16 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0917%, eas); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA1 c.547+14del?

BRCA1 c.547+14del is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA1 c.547+14del in the general population?

BRCA1 c.547+14del is ultra-rare (popmax 0.0917%, eas) (gnomAD).

BRCA1 c.547+14del

rs273902771 · VCV125880

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0917%, eas)

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +14	near-intronic (+14 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.96	GERP -0.17, phastCons 0.036
Overall
CADD	0.264	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0917% East Asian · 41/44,694 alleles

Filtering AF 0.0695% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0616%

Overall 0.00563% 89/1,579,848 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0917%	1,090
Remaining individualsnot grpmax-eligible	0.00815%	12,277
European (non-Finnish)	0.00357%	28,027
South Asian	0.00222%	45,146

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.547+14del
MANE Select: NM_007294
dbSNP: rs273902771
Type: Deletion
Location: chr17:43099761 (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

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast cancer breast-ovarian cancer, familial, susceptibility to, 1 hereditary neoplastic syndrome

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-547-plus-14del (accessed [today's date]).

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