BRF1 p.Pro292=
c.876C>G · rs369618475 · VCV719028
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.012 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.3 | GERP -3.1 |
| Overall | ||
| CADD | 0.038 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,886 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000372%
6/1,613,256 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,886 |
| Admixed American | 0.00167% | 59,992 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| Finnishnot grpmax-eligible | 0.00158% | 63,304 |
| European (non-Finnish) | 0.000169% | 589,991 |
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
- BRF1
- Protein
- p.Pro292=
- Coding
- c.876C>G
- MANE Select
- NM_004926 · reported on NM_001519
- dbSNP
- rs369618475
- Type
- single nucleotide variant
- Location
- chr14:105226673 (GRCh38)
- Structure
- AlphaFold pLDDT 59.70 · 2 PDB
- Residue 292
- the 'necessary for mrna decay activation' region; the 'disordered' region
Similar variants
- BRF1 p.Pro292His Pathogenic/Likely pathogenic ★★ same residue
- BRF1 p.Pro292Arg Likely pathogenic ★ same residue
- BRF1 p.Pro292Leu Uncertain significance ★ ⚠ same residue
- BRF1 p.Ser226Leu Pathogenic/Likely pathogenic ★★ same type
- BRF1 p.Ala565Ser Uncertain significance ★★ ⚠ same type
- BRF1 p.Arg213Lys Uncertain significance ★★ ⚠ same type
- BRF1 p.Arg216Gln Uncertain significance ★★ ⚠ same type
- BRF1 p.Arg261Gln Uncertain significance ★★ ⚠ same type
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/brf1-p-pro292 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown