BICD2 p.Gln654=
c.1962G>A · rs746391061 · VCV474268
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Conditions
2
Inborn genetic diseases
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 2.2 | GERP -0.52, phastCons 1 |
| Overall | ||
| CADD | 6.709 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,082 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00533%
Overall
0.00551%
89/1,614,008 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,041 |
| European (non-Finnish) | 0.00703% | 14,217 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| South Asian | 0.0022% | 45,547 |
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
- BICD2
- Protein
- p.Gln654=
- Coding
- c.1962G>A
- MANE Select
- NM_001003800
- dbSNP
- rs746391061
- Type
- single nucleotide variant
- Location
- chr9:92718683 (GRCh38)
- Gene constraint
- LOEUF 0.507 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 78.89 · 2 PDB
- Residue 654
- the 'interaction with ranbp2' region
Similar variants
- BICD2 p.Arg694Cys Pathogenic/Likely pathogenic ★★ same condition
- BICD2 p.Arg694Gly Pathogenic/Likely pathogenic ★★ same condition
- BICD2 p.Lys734Glu Likely pathogenic ★★ same condition
- BICD2 p.Ser107Leu Pathogenic ★★ ⚠ same condition
- BICD2 p.Thr703Met Pathogenic/Likely pathogenic ★★ same condition
- BICD2 p.Tyr538Cys Pathogenic ★★ ⚠ same condition
- BICD2 p.Tyr556Ser Likely pathogenic ★★ ⚠ same condition
- BICD2 c.1062+5G>A Uncertain significance ★★ 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/bicd2-p-gln654 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown