BRAT1 p.Pro384=
c.1152G>A · rs185653171 · VCV1112864
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.006%, amr)
Conditions
1
neonatal-onset encephalopathy with rigidity and seizures
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 1.4 | GERP -0.89, phastCons 1 |
| Overall | ||
| CADD | 12.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.006%
Admixed American · 3/49,986 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00106%
Overall
0.00142%
22/1,548,688 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.006% | 16,662 |
| African / African-American | 0.00545% | 18,341 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,818 |
| South Asian | 0.00118% | 84,516 |
| European (non-Finnish) | 0.00113% | 88,242 |
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
- BRAT1
- Protein
- p.Pro384=
- Coding
- c.1152G>A
- MANE Select
- NM_152743
- dbSNP
- rs185653171
- Type
- single nucleotide variant
- Location
- chr7:2541467 (GRCh38)
- Gene constraint
- LOEUF 1.39 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.28 · 5 PDB
Similar variants
- BRAT1 p.Pro384Leu Uncertain significance ★ ⚠ same residue
- BRAT1 c.1499-1G>T Pathogenic/Likely pathogenic ★★ same condition
- BRAT1 c.283-1G>A Likely pathogenic ★★ same condition
- BRAT1 p.Ala642Glu Likely pathogenic ★★ same condition
- BRAT1 p.Arg268His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- BRAT1 p.Arg427Ter Likely pathogenic ★★ same condition
- BRAT1 p.Arg562Ter Pathogenic/Likely pathogenic ★★ same condition
- BRAT1 p.Gln196Ter Pathogenic/Likely pathogenic ★★ same condition
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/brat1-p-pro384 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown