BRAT1 p.Pro323=
c.969C>A · rs1451106727 · VCV2170319
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00539%, afr)
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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.14 | GERP -3, phastCons 0.096 |
| Overall | ||
| CADD | 5.038 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00539%
African / African-American · 4/74,176 alleles
Filtering AF
0.00176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00105%
Overall
0.000254%
4/1,573,174 alleles · very rare
exomes 4/1,420,900 · genomes 0/152,274 · joint denominator
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.Pro323=
- Coding
- c.969C>A
- MANE Select
- NM_152743
- dbSNP
- rs1451106727
- Type
- single nucleotide variant
- Location
- chr7:2542166 (GRCh38)
- Gene constraint
- LOEUF 1.39 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.28 · 5 PDB
- Residue 323
- an α-helix
Similar variants
- BRAT1 p.Pro323Leu Likely pathogenic ★ 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-pro323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown