BSCL2 p.Ser255=
c.765G>A · rs774120735 · VCV1678788
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Conditions
1
Charcot-Marie-Tooth disease type 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.69 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.55 | gain · loss 0.25 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.98, phastCons 1 |
| Overall | ||
| CADD | 25.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,992 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00124%
20/1,613,876 alleles · very rare
exomes 19/1,461,708 · genomes 1/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,998 |
| South Asian | 0.00329% | 30,359 |
| African / African-American | 0.00133% | 74,926 |
| European (non-Finnish) | 0.00102% | 98,337 |
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.Ser255=
- Coding
- c.765G>A
- MANE Select
- NM_001122955
- dbSNP
- rs774120735
- Type
- single nucleotide variant
- Location
- chr11:62692663 (GRCh38)
- Gene constraint
- LOEUF 0.869 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.09 · 1 PDB
Similar variants
- BSCL2 p.Ser255Leu 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-ser255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown