BRF1 p.Asp643=
c.1929C>T · rs961802130 · VCV786751
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.7 | GERP -2.7 |
| Overall | ||
| CADD | 0.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,048 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.0018%
29/1,611,942 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,024 |
| African / African-American | 0.00802% | 12,475 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,812 |
| European (non-Finnish) | 0.00153% | 65,545 |
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.Asp643=
- Coding
- c.1929C>T
- MANE Select
- NM_004926 · reported on NM_001519
- dbSNP
- rs961802130
- Type
- single nucleotide variant
- Location
- chr14:105211189 (GRCh38)
- Structure
- AlphaFold pLDDT 59.70 · 2 PDB
Similar variants
- BRF1 p.Asp643Glu Uncertain significance ★ ⚠ same residue
- 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
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-asp643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown