BRAT1 p.Pro503=
c.1509T>C · rs1159646565 · VCV1590018
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00173%, 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 -1.8 | GERP -3.4 |
| Overall | ||
| CADD | 4.661 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00173%
Admixed American · 1/57,650 alleles
Overall
6.93e-05%
1/1,442,082 alleles · very rare
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.Pro503=
- Coding
- c.1509T>C
- MANE Select
- NM_152743
- dbSNP
- rs1159646565
- Type
- single nucleotide variant
- Location
- chr7:2539632 (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 503
- an α-helix
Similar variants
- BRAT1 p.Pro503Leu Uncertain significance ★★ ⚠ same residue
- BRAT1 p.Pro503Ser Conflicting classifications of pathogenicity ★ ⚠ 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
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-pro503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown