BRF1 p.Val309=
c.927C>T · rs117732489 · VCV708602
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.75%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.086 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.14 | GERP -3.5, phastCons 0.83 |
| Overall | ||
| CADD | 5.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.75%
European (non-Finnish) · 8,855/1,180,008 alleles
Filtering AF
0.737%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.732%
Overall
0.6%
9,689/1,614,052 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.75% | 133 |
| Remaining individualsnot grpmax-eligible | 0.493% | 203 |
| Finnishnot grpmax-eligible | 0.388% | 258 |
| Admixed American | 0.272% | 368 |
| African / African-American | 0.127% | 790 |
| Middle Eastern | 0.099% | 1,010 |
| South Asian | 0.0121% | 8,281 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
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.Val309=
- Coding
- c.927C>T
- MANE Select
- NM_004926 · reported on NM_001519
- dbSNP
- rs117732489
- Type
- single nucleotide variant
- Location
- chr14:105226279 (GRCh38)
- Structure
- AlphaFold pLDDT 59.70 · 2 PDB
- Residue 309
- the 'necessary for mrna decay activation' region; the 'disordered' region
Similar variants
- BRF1 p.Pro292His Pathogenic/Likely pathogenic ★★ same type
- 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
- BRF1 p.Arg302Trp Uncertain significance ★★ ⚠ same type
- BRF1 p.Gly402Ser 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-val309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown