BRIP1 p.Gln491=
c.1473G>A · rs2145238730 · VCV1773409
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.52e-05%, 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 | ||
| SpliceAI | Δ0.45 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.26 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 20.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.52e-05%
European (non-Finnish) · 1/1,174,182 alleles
Overall
6.89e-05%
1/1,450,784 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
- Protein
- p.Gln491=
- Coding
- c.1473G>A
- MANE Select
- NM_032043
- dbSNP
- rs2145238730
- Type
- single nucleotide variant
- Location
- chr17:61793597 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.19 · 6 PDB
Similar variants
- BRIP1 p.Gln491Ter Pathogenic/Likely pathogenic ★★ same residue
- BRIP1 p.Gln491Arg Uncertain significance ★★ ⚠ same residue
- BRIP1 p.Gln491Leu Uncertain significance ★★ ⚠ same residue
- BRIP1 p.Gln491His Uncertain significance ★ ⚠ same residue
- BRIP1 p.Gln491Pro Uncertain significance ★ ⚠ same residue
- BRIP1 p.Gln491fs Pathogenic ★ same residue
- BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
- BRIP1 c.1141-2A>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-p-gln491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown