Is BRIP1 p.Asp770= (c.2310T>C) pathogenic?

BRIP1 p.Asp770= (c.2310T>C) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00267%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Asp770= (c.2310T>C)?

BRIP1 p.Asp770= (c.2310T>C) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Asp770= (c.2310T>C) in the general population?

BRIP1 p.Asp770= (c.2310T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

BRIP1 p.Asp770=

c.2310T>C · rs148752066 · VCV136576

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 4.6	GERP 2.1, phastCons 1
Overall
CADD	9.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,906 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000372% 6/1,613,836 alleles · very rare exomes 4/1,461,676 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,453
European (non-Finnish)	0.000339%	294,972

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.Asp770=
Coding: c.2310T>C
MANE Select: NM_032043
dbSNP: rs148752066
Type: single nucleotide variant
Location: chr17:61743082 (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

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.Asp770Tyr Uncertain significance ★★ ⚠ same residue
BRIP1 p.Asp770Asn Uncertain significance ★ ⚠ same residue
BRIP1 p.Asp770Gly 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-asp770 (accessed [today's date]).

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