BSCL2 p.Trp321Ter
c.963G>A · VCV3658282
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
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. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 7 of 11 |
| Splicing | ||
| SpliceAI | Δ0.79 | donor loss · deltas |
| Pangolin | Δ0.68 | gain · loss 0.56 · SpliceAI calls loss · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 43.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- BSCL2
- Protein
- p.Trp321Ter
- Coding
- c.963G>A
- MANE Select
- NM_001122955
- Type
- single nucleotide variant
- Location
- chr11:62691322 (GRCh38)
- Gene constraint
- LOEUF 0.869 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.09 · 1 PDB
- Residue 321
- the 'disordered' region
Similar variants
- 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
- BSCL2 p.Ser154Trp 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-trp321ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown