Is BRIP1 p.Pro210fs (c.627dup) pathogenic?

BRIP1 p.Pro210fs (c.627dup) is classified Pathogenic/Likely pathogenic in BRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-31). Very rare (popmax 0.00134%, afr); Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Pro210fs (c.627dup)?

BRIP1 p.Pro210fs (c.627dup) is associated with hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Pro210fs (c.627dup) in the general population?

BRIP1 p.Pro210fs (c.627dup) is very rare (popmax 0.00134%, afr) (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.Pro210fs

c.627dup · rs1392582030 · VCV2583421

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1.3, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,904 alleles

Overall 0.000657% 1/152,206 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.Pro210fs
Coding: c.627dup
MANE Select: NM_032043
dbSNP: rs1392582030
Type: Duplication
Location: chr17:61847100 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 210: the helicase atp-binding domain

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

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRIP1 p.Pro210Leu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Pro210= Benign/Likely benign ★★ same residue
BRIP1 p.Pro210His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Pro210Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro210fs (accessed [today's date]).

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