Is OSBPL2 p.Ter481= (c.1442G>A) pathogenic?

OSBPL2 p.Ter481= (c.1442G>A) is classified Likely benign in OSBPL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Ultra-rare (popmax 0.0164%, mid).

How common is OSBPL2 p.Ter481= (c.1442G>A) in the general population?

OSBPL2 p.Ter481= (c.1442G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

OSBPL2 p.Ter481=

c.1442G>A · rs775473641 · VCV1608002

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.046	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP -4.8, phastCons 1
Overall
CADD	12.41	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00217% 35/1,613,278 alleles · ultra-rare exomes 33/1,461,030 · genomes 2/152,248 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.008%	12,493
Admixed American	0.00668%	14,972
European (non-Finnish)	0.00212%	47,191

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.Ter481=
Coding: c.1442G>A
MANE Select: NM_144498
dbSNP: rs775473641
Type: single nucleotide variant
Location: chr20:62293886 (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

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-ter481 (accessed [today's date]).

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