BRF1 p.Asp648=
c.1944C>T · rs752216291 · VCV757033
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, amr)
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 -1.7 | GERP -2.7 |
| Overall | ||
| CADD | 2.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/59,970 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00786%
Overall
0.00136%
22/1,612,320 alleles · ultra-rare
exomes 14/1,460,264 · genomes 8/152,056 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,452 |
| African / African-American | 0.00401% | 24,959 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,452 |
| European (non-Finnish) | 0.000593% | 168,554 |
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.Asp648=
- Coding
- c.1944C>T
- MANE Select
- NM_001519
- dbSNP
- rs752216291
- Type
- single nucleotide variant
- Location
- chr14:105211174 (GRCh38)
- Structure
- AlphaFold pLDDT 59.70 · 2 PDB
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-asp648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown