Is BRIP1 c.2575+2dup pathogenic?

BRIP1 c.2575+2dup is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-06-09). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 c.2575+2dup?

BRIP1 c.2575+2dup is associated with hereditary breast carcinoma, hereditary breast ovarian cancer syndrome, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 c.2575+2dup in the general population?

BRIP1 c.2575+2dup is absent from gnomAD (gnomAD).

How is Hereditary breast cancer inherited?

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

BRIP1 c.2575+2dup

rs1555574711 · VCV491448

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 2, phastCons 1
Non-coding constraint	Z 4.23	1 kb window · o/e 0.71 · regional · uncalibrated

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: BRIP1
Coding: c.2575+2dup
MANE Select: NM_032043
dbSNP: rs1555574711
Type: Duplication
Location: chr17:61693427 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

Full BRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: hereditary breast ovarian cancer syndrome Fanconi anemia complementation group J hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BRIP1 c.2492+2dup Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Ala27fs Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Ala551fs Pathogenic ★★ same condition
BRIP1 p.Ala759fs Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Ala841fs Pathogenic ★★ same condition
BRIP1 p.Arg416fs Pathogenic ★★ same condition
BRIP1 p.Arg658fs Pathogenic ★★ same condition
BRIP1 p.Arg798fs 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/brip1-c-2575-plus-2dup (accessed [today's date]).

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