Is BRIP1 p.Pro244Arg (c.731C>G) pathogenic?

BRIP1 p.Pro244Arg (c.731C>G) is classified Uncertain significance in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-05). AlphaMissense: ambiguous (0.5226); Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Pro244Arg (c.731C>G)?

BRIP1 p.Pro244Arg (c.731C>G) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Pro244Arg (c.731C>G) in the general population?

BRIP1 p.Pro244Arg (c.731C>G) 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.

What do computational predictors say about BRIP1 p.Pro244Arg (c.731C>G)?

AlphaMissense predicts ambiguous (score 0.5226) — an in-silico prediction, not a clinical call.

BRIP1 p.Pro244Arg

c.731C>G · rs2145419213 · VCV1407553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5226 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.5226	ambiguous
REVEL	0.593	indeterminate
SaProt	LLR -12.48	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 68 kb · p 0.065 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro244Arg
Coding: c.731C>G
MANE Select: NM_032043
dbSNP: rs2145419213
Type: single nucleotide variant
Location: chr17:61808654 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 244: 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

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRIP1 p.Pro244Ala Uncertain significance ★★ ⚠ same residue
BRIP1 p.Pro244Ser Uncertain significance ★★ same residue
BRIP1 p.Pro244= Benign/Likely benign ★★ same residue
BRIP1 p.Pro244_Ile246del 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-pro244arg (accessed [today's date]).

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