OSBPL2 p.Pro65=
c.195G>A · rs148250350 · VCV2892345
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0374%, afr)
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 -10 | GERP -5.1 |
| Overall | ||
| CADD | 0.231 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0374%
African / African-American · 28/74,912 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0229%
Overall
0.0103%
167/1,613,986 alleles · ultra-rare
exomes 151/1,461,820 · genomes 16/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0374% | 2,675 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0203% | 4,934 |
| European (non-Finnish) | 0.0109% | 9,147 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00167% | 60,002 |
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.Pro65=
- Coding
- c.195G>A
- MANE Select
- NM_144498
- dbSNP
- rs148250350
- Type
- single nucleotide variant
- Location
- chr20:62263628 (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.Pro65Leu Uncertain significance ★ same residue
- 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
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-pro65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown