BICRA p.Pro727=
c.2181G>C · rs200583519 · VCV2650171
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.587%, afr)
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 4 | GERP 3.6, phastCons 1 |
| Overall | ||
| CADD | 9.977 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.587%
African / African-American · 427/72,698 alleles
Filtering AF
0.541%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.523%
Overall
0.0296%
455/1,535,486 alleles · rare
exomes 201/1,384,364 · genomes 254/151,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.587% | 170 |
| Remaining individualsnot grpmax-eligible | 0.0235% | 4,260 |
| Admixed American | 0.0148% | 6,756 |
| South Asian | 0.0059% | 16,947 |
| European (non-Finnish) | 8.81e-05% | 1,134,675 |
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
- BICRA
- Protein
- p.Pro727=
- Coding
- c.2181G>C
- MANE Select
- NM_001394372
- dbSNP
- rs200583519
- Type
- single nucleotide variant
- Location
- chr19:47682050 (GRCh38)
- Gene constraint
- LOEUF 0.659 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 42.79
- Residue 727
- the 'disordered' region; a UniProt-annotated variant site (in css12)
Similar variants
- BICRA p.Pro727Leu Uncertain significance ★ ⚠ same residue
- BICRA p.Gln290Ter Pathogenic/Likely pathogenic ★★ same type
- BICRA p.Ala1110Thr Uncertain significance ★★ ⚠ same type
- BICRA p.Ala313Pro Uncertain significance ★★ ⚠ same type
- BICRA p.Ala579Thr Uncertain significance ★★ ⚠ same type
- BICRA p.Arg1384Cys Uncertain significance ★★ ⚠ same type
- BICRA p.Arg802Cys Uncertain significance ★★ ⚠ same type
- BICRA p.Asn408Lys 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/bicra-p-pro727 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown