Is BRIP1 p.Trp63Ter (c.188G>A) pathogenic?

BRIP1 p.Trp63Ter (c.188G>A) is classified Pathogenic/Likely pathogenic in BRIP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-05). Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Trp63Ter (c.188G>A)?

BRIP1 p.Trp63Ter (c.188G>A) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Trp63Ter (c.188G>A) in the general population?

BRIP1 p.Trp63Ter (c.188G>A) is absent from gnomAD v4.1 (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.Trp63Ter

c.188G>A · rs1603367649 · VCV820224

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,730)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Overall
CADD	38.0	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

No allele count reported in gnomAD v4.1 (AN 1,612,730). 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.Trp63Ter
Coding: c.188G>A
MANE Select: NM_032043
dbSNP: rs1603367649
Type: single nucleotide variant
Location: chr17:61859813 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 63: 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

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.Trp63Arg Uncertain significance ★★ ⚠ same residue
BRIP1 p.Trp63Cys Uncertain significance ★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>C Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>G Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>T Likely pathogenic ★★ same condition
BRIP1 c.1340+1G>A Pathogenic/Likely pathogenic ★★ same condition
BRIP1 c.1341-1G>A 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-trp63ter (accessed [today's date]).

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