Is BRIP1 p.Gln102Arg (c.305A>G) pathogenic?

BRIP1 p.Gln102Arg (c.305A>G) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-05). AlphaMissense: likely benign (0.069); Very rare (popmax 0.00669%, eas); Associated with familial ovarian cancer.

What condition is associated with BRIP1 p.Gln102Arg (c.305A>G)?

BRIP1 p.Gln102Arg (c.305A>G) is associated with familial ovarian cancer, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Gln102Arg (c.305A>G) in the general population?

BRIP1 p.Gln102Arg (c.305A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about BRIP1 p.Gln102Arg (c.305A>G)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

BRIP1 p.Gln102Arg

c.305A>G · rs1484234707 · VCV479416

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -1.9, phastCons 0.5
Regional constraint	o/e 0.92	unconstrained · MANE · 68 kb · p 0.065 · regional, not allelic
Overall
CADD	13.99	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

Grpmax group 0.00669% East Asian · 3/44,868 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000616% 9/1,461,770 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,956
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.000424%	235,992

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.Gln102Arg
Coding: c.305A>G
MANE Select: NM_032043
dbSNP: rs1484234707
Type: single nucleotide variant
Location: chr17:61857132 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 102: the helicase atp-binding domain; the 'disordered' region

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

Disease context

familial ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Gln102Ter Pathogenic ★★ same residue
BRIP1 p.Gln102Leu Uncertain significance ★ ⚠ same residue
BRIP1 p.Gln102= Likely benign ★ 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

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-gln102arg (accessed [today's date]).

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