Is BRIP1 p.Asp744= (c.2232C>T) pathogenic?

BRIP1 p.Asp744= (c.2232C>T) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0495%, mid); Associated with familial ovarian cancer.

What condition is associated with BRIP1 p.Asp744= (c.2232C>T)?

BRIP1 p.Asp744= (c.2232C>T) is associated with familial ovarian cancer, ovarian cancer, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Asp744= (c.2232C>T) in the general population?

BRIP1 p.Asp744= (c.2232C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

BRIP1 p.Asp744=

c.2232C>T · rs374362388 · VCV182353

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

familial ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.8, phastCons 1
Overall
CADD	6.531	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,056 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00607% 98/1,613,654 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Admixed American	0.0183%	5,453
East Asian	0.0112%	8,963
South Asian	0.00659%	15,176
European (non-Finnish)	0.00475%	21,069
African / African-American	0.004%	24,969
Finnishnot grpmax-eligible	0.00156%	63,958

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.Asp744=
Coding: c.2232C>T
MANE Select: NM_032043
dbSNP: rs374362388
Type: single nucleotide variant
Location: chr17:61744457 (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: ovarian cancer Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Asp744Glu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Asp744His Uncertain significance ★★ ⚠ same residue
BRIP1 p.Asp744Val 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

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-asp744 (accessed [today's date]).

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