Is OSBPL2 p.Asp342= (c.1026C>T) pathogenic?

OSBPL2 p.Asp342= (c.1026C>T) is classified Likely benign in OSBPL2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-29). Ultra-rare (popmax 0.0546%, afr); Associated with Inborn genetic diseases.

What condition is associated with OSBPL2 p.Asp342= (c.1026C>T)?

OSBPL2 p.Asp342= (c.1026C>T) is associated with Inborn genetic diseases (ClinVar).

How common is OSBPL2 p.Asp342= (c.1026C>T) in the general population?

OSBPL2 p.Asp342= (c.1026C>T) is ultra-rare (popmax 0.0546%, afr) (gnomAD).

OSBPL2 p.Asp342=

c.1026C>T · rs140864045 · VCV1678834

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, afr)

Conditions

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 -14	GERP -5
Overall
CADD	0.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0546% African / African-American · 41/75,056 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.0031% 50/1,613,628 alleles · ultra-rare exomes 30/1,461,284 · genomes 20/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0546%	1,831
Admixed American	0.00333%	30,014
Remaining individualsnot grpmax-eligible	0.0016%	62,496
South Asian	0.0011%	91,078
European (non-Finnish)	0.000424%	235,956

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.Asp342=
Coding: c.1026C>T
MANE Select: NM_144498
dbSNP: rs140864045
Type: single nucleotide variant
Location: chr20:62286612 (GRCh38)
Gene constraint: LOEUF 0.467 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 83.92 · 1 PDB

Full OSBPL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OSBPL2 p.Arg434Trp Uncertain significance ★★ same condition
OSBPL2 p.Asp475Asn Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Gln58Pro Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Glu284Gly Uncertain significance ★★ same condition
OSBPL2 p.Gly245Arg Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Ile34Val Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Ile479Thr Uncertain significance ★★ ⚠ same condition
OSBPL2 p.Lys203Gln 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/osbpl2-p-asp342 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown