BRWD1 p.Phe397=
c.1191T>C · VCV3770488
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
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 2.1 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 9.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,060 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0295%
Overall
0.011%
177/1,614,032 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| European (non-Finnish) | 0.0135% | 7,421 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,812 |
| Admixed American | 0.00167% | 60,020 |
| Finnishnot grpmax-eligible | 0.00156% | 63,986 |
| African / African-American | 0.00133% | 75,034 |
| South Asian | 0.0011% | 91,080 |
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
- BRWD1
- Protein
- p.Phe397=
- Coding
- c.1191T>C
- MANE Select
- NM_033656
- Type
- single nucleotide variant
- Location
- chr21:39274427 (GRCh38)
- Gene constraint
- LOEUF 0.447 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.20 · 1 PDB
Similar variants
- BRWD1 c.50-14T>C Benign ★★ same type
- BRWD1 p.Asn2173= Likely benign ★★ same type
- BRWD1 p.Leu1699Pro Benign ★★ same type
- BRWD1 p.Ser1511Pro Benign ★★ same type
- BRWD1 p.Arg219His Likely pathogenic ★ same type
- BRWD1 p.Gln1858Leu Likely pathogenic ★ ⚠ same type
- BRWD1 c.2893-1G>T Uncertain significance ★ same type
- BRWD1 c.*8854G>C 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/brwd1-p-phe397 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown