Is BRIP1 p.Lys915fs (c.2742_2749del) pathogenic?

BRIP1 p.Lys915fs (c.27422749del) is classified Pathogenic in BRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-05). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Lys915fs (c.2742_2749del)?

BRIP1 p.Lys915fs (c.2742_2749del) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Lys915fs (c.2742_2749del) in the general population?

BRIP1 p.Lys915fs (c.2742_2749del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Hereditary breast cancer inherited?

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

BRIP1 p.Lys915fs

c.2742_2749del · rs2144112699 · VCV1459574

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 19 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.8	GERP -4.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,928 alleles

Overall 6.84e-05% 1/1,461,746 alleles · very rare

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: BRIP1
Protein: p.Lys915fs
Coding: c.2742_2749del
MANE Select: NM_032043
dbSNP: rs2144112699
Type: Deletion
Location: chr17:61685992 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 915: the 'interaction with brca1' region

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: Fanconi anemia complementation group J hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRIP1 p.Lys915= Benign/Likely benign ★★ same residue
BRIP1 c.1629-3_1634del Likely pathogenic ★★ same condition
BRIP1 c.1936del Pathogenic ★★ same condition
BRIP1 c.205+1del Pathogenic/Likely pathogenic ★★ same condition
BRIP1 c.2257+2_2257+8del Likely pathogenic ★★ same condition
BRIP1 c.2370_2379+20del Likely pathogenic ★★ same condition
BRIP1 c.2492_2492+5del Likely pathogenic ★★ same condition
BRIP1 c.2492+1del Likely 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-p-lys915fs (accessed [today's date]).

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