BSCL2 p.Arg331His
c.992G>A · rs201229787 · VCV576407
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0761 | likely benign |
|---|---|---|
| REVEL | 0.34 | indeterminate |
| SaProt | LLR -7.04 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 0.83 | GERP 0.21, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 2,047 bp · p 0.6 · regional, not allelic |
| Overall | ||
| CADD | 23.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R267H vs ClinVar R331H) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0507% | 1,974 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,501 |
| Admixed American | 0.00167% | 60,012 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000678% | 147,502 |
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
- BSCL2
- Protein
- p.Arg331His
- Coding
- c.992G>A
- MANE Select
- NM_001122955
- dbSNP
- rs201229787
- Type
- single nucleotide variant
- Location
- chr11:62691293 (GRCh38)
- Gene constraint
- LOEUF 0.869 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.09 · 1 PDB
- Residue 331
- the 'disordered' region
Similar variants
- BSCL2 p.Arg331Cys Uncertain significance ★★ ⚠ same residue
- BSCL2 c.1006-2A>C Likely pathogenic ★★ same condition
- BSCL2 c.486+1G>A Pathogenic/Likely pathogenic ★★ same condition
- BSCL2 p.Ala276Pro Pathogenic ★★ same condition
- BSCL2 p.Arg329Ter Pathogenic ★★ same condition
- BSCL2 p.Asn152Ser Pathogenic ★★ ⚠ same condition
- BSCL2 p.Glu253Ter Pathogenic ★★ same condition
- BSCL2 p.Ser154Leu 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/bscl2-p-arg331his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown