Is BRIP1 p.Pro114= (c.342A>G) pathogenic?

BRIP1 p.Pro114= (c.342A>G) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-17). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Pro114= (c.342A>G)?

BRIP1 p.Pro114= (c.342A>G) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Pro114= (c.342A>G) in the general population?

BRIP1 p.Pro114= (c.342A>G) is absent from gnomAD v4.1 (gnomAD).

BRIP1 p.Pro114=

c.342A>G · rs756764576 · VCV632724

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.78	GERP -4.2, phastCons 0.002
Overall
CADD	9.623	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRIP1
Protein: p.Pro114=
Coding: c.342A>G
MANE Select: NM_032043
dbSNP: rs756764576
Type: single nucleotide variant
Location: chr17:61857095 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 114: the helicase atp-binding domain; the 'disordered' region

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

Also linked: Fanconi anemia complementation group J hereditary breast carcinoma

Similar variants

BRIP1 p.Pro114Gln Uncertain significance ★★ ⚠ same residue
BRIP1 p.Pro114Leu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Pro114Ser Uncertain significance ★★ ⚠ same residue
BRIP1 p.Pro114Ala 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

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-pro114 (accessed [today's date]).

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