OSBPL2 p.Ser336=
c.1008C>T · VCV4945566
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3.4 |
| Overall | ||
| CADD | 0.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,080 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.00316%
51/1,613,058 alleles · ultra-rare
exomes 45/1,460,872 · genomes 6/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,040 |
| South Asian | 0.0231% | 4,336 |
| Admixed American | 0.01% | 9,997 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,489 |
| African / African-American | 0.00267% | 37,455 |
| Finnishnot grpmax-eligible | 0.00157% | 63,706 |
| European (non-Finnish) | 0.00119% | 84,250 |
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.Ser336=
- Coding
- c.1008C>T
- MANE Select
- NM_144498
- Type
- single nucleotide variant
- Location
- chr20:62286594 (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.Ser336Ala 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-ser336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown