BICRA p.Pro653=
c.1959A>C · rs1272457441 · VCV2650168
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.529%, amr)
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 -9.4 | GERP -8.4 |
| Overall | ||
| CADD | 0.049 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.529%
Admixed American · 146/27,606 alleles
Filtering AF
0.459%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.432%
Overall
0.0478%
519/1,085,620 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.529% | 189 |
| Amishnot grpmax-eligible | 0.244% | 410 |
| South Asian | 0.134% | 748 |
| Ashkenazi Jewishnot grpmax-eligible | 0.123% | 811 |
| Finnishnot grpmax-eligible | 0.105% | 952 |
| Middle Eastern | 0.0666% | 1,501 |
| Remaining individualsnot grpmax-eligible | 0.0572% | 1,749 |
| East Asian | 0.0451% | 2,216 |
| African / African-American | 0.0356% | 2,813 |
| European (non-Finnish) | 0.0243% | 4,111 |
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.Pro653=
- Coding
- c.1959A>C
- MANE Select
- NM_001394372
- dbSNP
- rs1272457441
- Type
- single nucleotide variant
- Location
- chr19:47681129 (GRCh38)
- Gene constraint
- LOEUF 0.659 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 42.79
- Residue 653
- the 'disordered' region
Similar variants
- BICRA p.Pro653Gln 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-pro653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown