BRF1 p.Ala18=
c.54G>C · VCV4534211
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.118%, afr)
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 -0.12 | GERP -0.18, phastCons 0.71 |
| Overall | ||
| CADD | 12.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.118%
African / African-American · 81/68,704 alleles
Filtering AF
0.0971%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0895%
Overall
0.00946%
141/1,490,292 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.118% | 848 |
| Admixed American | 0.0333% | 3,000 |
| Middle Eastern | 0.0227% | 4,396 |
| Remaining individualsnot grpmax-eligible | 0.0226% | 4,423 |
| European (non-Finnish) | 0.00276% | 36,254 |
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.Ala18=
- Coding
- c.54G>C
- MANE Select
- NM_004926 · reported on NM_001519
- Type
- single nucleotide variant
- Location
- chr14:105300576 (GRCh38)
- Structure
- AlphaFold pLDDT 59.70 · 2 PDB
- Residue 18
- the 'necessary and sufficient for the association with mrna decay enzymes and mrna decay activation' region
Similar variants
- PACS2 p.Thr18Met Uncertain significance ★ ⚠ same residue
- PACS2 p.Thr18= Likely benign ★ 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
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-ala18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown