BICD2 p.Leu198Pro
c.593T>C · VCV3342840
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9983 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9983 | likely pathogenic ✓ concordant with ClinVar · top 1% in BICD2 |
|---|---|---|
| REVEL | 0.799 | moderately pathogenic-leaning |
| SaProt | LLR -13.93 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 0.20 | constrained · MANE · 1,967 bp · p 8e-05 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- BICD2
- Protein
- p.Leu198Pro
- Coding
- c.593T>C
- MANE Select
- NM_001003800
- Type
- single nucleotide variant
- Location
- chr9:92722669 (GRCh38)
- Gene constraint
- LOEUF 0.507 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 78.89 · 2 PDB
- Residue 198
- the 'interacts with dynll1, dync1h1, dync1i2, dctn1 and dctn2' region
Similar variants
- BICD2 p.Arg694Cys Pathogenic/Likely pathogenic ★★ same type
- BICD2 p.Arg694Gly Pathogenic/Likely pathogenic ★★ same type
- BICD2 p.Arg694His Pathogenic/Likely pathogenic ★★ same type
- BICD2 p.Glu774Lys Pathogenic/Likely pathogenic ★★ same type
- BICD2 p.Lys734Glu Likely pathogenic ★★ same type
- BICD2 p.Ser107Leu Pathogenic ★★ ⚠ same type
- BICD2 p.Thr703Met Pathogenic/Likely pathogenic ★★ same type
- BICD2 p.Tyr538Cys Pathogenic ★★ ⚠ 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/bicd2-p-leu198pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown