Is BRIP1 p.Arg814His (c.2441G>A) pathogenic?

BRIP1 p.Arg814His (c.2441G>A) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1064); Very rare (popmax 0.0045%, nfe); Associated with familial ovarian cancer.

What condition is associated with BRIP1 p.Arg814His (c.2441G>A)?

BRIP1 p.Arg814His (c.2441G>A) is associated with familial ovarian cancer, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRIP1 p.Arg814His (c.2441G>A) in the general population?

BRIP1 p.Arg814His (c.2441G>A) is very rare (popmax 0.0045%, nfe) (gnomAD).

What do computational predictors say about BRIP1 p.Arg814His (c.2441G>A)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

BRIP1 p.Arg814His

c.2441G>A · rs45468199 · VCV141744

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0045%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.0045% European (non-Finnish) · 53/1,177,258 alleles

Filtering AF 0.00351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00371% 54/1,456,798 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0045%	22,212
South Asian	0.00111%	89,964

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.Arg814His
Coding: c.2441G>A
MANE Select: NM_032043
dbSNP: rs45468199
Type: single nucleotide variant
Location: chr17:61716002 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

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: hereditary breast ovarian cancer syndrome breast cancer ovarian cancer Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Arg814Gly Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg814Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Arg814Pro Uncertain significance ★ ⚠ same residue
BRIP1 p.Arg814Ser 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-arg814his (accessed [today's date]).

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