BRIP1 c.2575+4A>G
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000255%, nfe)
Conditions
3
Fanconi anemia complementation group J
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.59 | donor loss, 4 bp away · masked 0 · deltas |
| Pangolin | Δ0.56 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP 0.74, phastCons 1 |
| Non-coding constraint | Z 4.23 | 1 kb window · o/e 0.71 · regional · uncalibrated |
| Overall | ||
| CADD | 17.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000255%
European (non-Finnish) · 3/1,176,934 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,610,566 alleles · very rare
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
- Coding
- c.2575+4A>G
- MANE Select
- NM_032043
- dbSNP
- rs758858747
- Type
- single nucleotide variant
- Location
- chr17:61693426 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.19 · 6 PDB
Similar variants
- 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
- BRIP1 c.1341-1G>A Likely pathogenic ★★ same condition
- BRIP1 c.1341-1G>C Likely pathogenic ★★ same condition
- BRIP1 c.1341-2A>C 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-c-2575-plus-4a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown