Is BRIP1 p.Val193fs (c.576dup) pathogenic?

BRIP1 p.Val193fs (c.576dup) is classified Pathogenic in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-05). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Val193fs (c.576dup)?

BRIP1 p.Val193fs (c.576dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Val193fs (c.576dup) in the general population?

BRIP1 p.Val193fs (c.576dup) is no gnomAD frequency available for this variant (gnomAD).

BRIP1 p.Val193fs

c.576dup · rs2078747114 · VCV920888

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

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 6 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.47	GERP -4.4

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.Val193fs
Coding: c.576dup
MANE Select: NM_032043
dbSNP: rs2078747114
Type: Duplication
Location: chr17:61847151 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 193: the helicase atp-binding domain; a UniProt-annotated variant site (in)

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

Disease context

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

Similar variants

BRIP1 p.Val193Ile Benign/Likely benign ★★ same residue
BRIP1 p.Val193_Leu195delinsGlu Uncertain significance ★ 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
BRIP1 p.Ala841fs Pathogenic ★★ same condition
BRIP1 p.Arg416fs 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-val193fs (accessed [today's date]).

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