Is BRIP1 p.Leu719fs (c.2156del) pathogenic?

BRIP1 p.Leu719fs (c.2156del) is classified Pathogenic in BRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-16). Absent from gnomAD; Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Leu719fs (c.2156del)?

BRIP1 p.Leu719fs (c.2156del) is associated with Fanconi anemia complementation group J, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Leu719fs (c.2156del) in the general population?

BRIP1 p.Leu719fs (c.2156del) is absent from gnomAD (gnomAD).

BRIP1 p.Leu719fs

c.2156del · rs2544838229 · VCV2774996

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fanconi anemia complementation group J

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 15 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.99	GERP 0.55, phastCons 1

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
Protein: p.Leu719fs
Coding: c.2156del
MANE Select: NM_032043
dbSNP: rs2544838229
Type: Deletion
Location: chr17:61744533 (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

Fanconi anemia complementation group J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Leu719= Conflicting classifications of pathogenicity ★ same residue
BRIP1 p.Leu719Phe Uncertain significance ★ ⚠ 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

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-leu719fs (accessed [today's date]).

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