BRF1 p.Ala232=
c.696G>A · rs142328073 · VCV788122
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.314%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.093 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.5 | GERP -3.1 |
| Overall | ||
| CADD | 0.017 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.314%
Middle Eastern · 19/6,060 alleles
Filtering AF
0.222%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.209%
Overall
0.131%
2,108/1,613,420 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.314% | 319 |
| Admixed American | 0.255% | 392 |
| Finnishnot grpmax-eligible | 0.235% | 425 |
| South Asian | 0.213% | 469 |
| Remaining individualsnot grpmax-eligible | 0.202% | 496 |
| African / African-American | 0.164% | 610 |
| East Asian | 0.118% | 847 |
| European (non-Finnish) | 0.109% | 920 |
| Ashkenazi Jewishnot grpmax-eligible | 0.027% | 3,701 |
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.Ala232=
- Coding
- c.696G>A
- MANE Select
- NM_004926 · reported on NM_001519
- dbSNP
- rs142328073
- Type
- single nucleotide variant
- Location
- chr14:105228912 (GRCh38)
- Structure
- AlphaFold pLDDT 59.70 · 2 PDB
- Residue 232
- the 'necessary for mrna decay activation' region
Similar variants
- BRF1 p.Ala232Pro 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-ala232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown