OSBPL2 p.Ser474=
c.1422C>T · VCV4751206
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0283%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.065 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -5.2 |
| Overall | ||
| CADD | 11.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0283%
Admixed American · 17/59,990 alleles
Filtering AF
0.018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.00198%
32/1,613,838 alleles · ultra-rare
exomes 31/1,461,606 · genomes 1/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0283% | 3,529 |
| South Asian | 0.00329% | 30,360 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| European (non-Finnish) | 0.000932% | 107,268 |
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
- OSBPL2
- Protein
- p.Ser474=
- Coding
- c.1422C>T
- MANE Select
- NM_144498
- Type
- single nucleotide variant
- Location
- chr20:62293866 (GRCh38)
- Gene constraint
- LOEUF 0.467 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.92 · 1 PDB
Similar variants
- OSBPL2 p.Ala442Val Uncertain significance ★★ ⚠ same type
- OSBPL2 p.Arg434Trp Uncertain significance ★★ same type
- OSBPL2 p.Asp475Asn Uncertain significance ★★ ⚠ same type
- OSBPL2 p.Gln125Pro Uncertain significance ★★ ⚠ same type
- OSBPL2 p.Gln58Pro Uncertain significance ★★ ⚠ same type
- OSBPL2 p.Glu284Gly Uncertain significance ★★ same type
- OSBPL2 p.Gly149Ser Uncertain significance ★★ ⚠ same type
- OSBPL2 p.Gly245Arg Uncertain significance ★★ ⚠ 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/osbpl2-p-ser474 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown