Is OSBP p.Pro685Arg (c.2054C>G) pathogenic?

OSBP p.Pro685Arg (c.2054C>G) is classified Uncertain significance in OSBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.2043); Absent from gnomAD v4.1.

How common is OSBP p.Pro685Arg (c.2054C>G) in the general population?

OSBP p.Pro685Arg (c.2054C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OSBP p.Pro685Arg (c.2054C>G)?

AlphaMissense predicts likely benign (score 0.2043) — an in-silico prediction, not a clinical call.

OSBP p.Pro685Arg

c.2054C>G · rs2495290853 · VCV3207001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2043 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2043	likely benign
REVEL	0.661	pathogenic-leaning
SaProt	LLR -9.06	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 3,663 bp · p 2e-07 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OSBP
Protein: p.Pro685Arg
Coding: c.2054C>G
MANE Select: NM_002556
dbSNP: rs2495290853
Type: single nucleotide variant
Location: chr11:59578155 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB
Residue 685: an α-helix

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

Similar variants

OSBP c.1557+10C>T Benign ★★ same type
OSBP p.Glu189= Benign ★★ same type
OSBP p.Ala271Ser Uncertain significance ★ ⚠ same type
OSBP p.Ala90Ser Uncertain significance ★ ⚠ same type
OSBP p.Arg171His Uncertain significance ★ ⚠ same type
OSBP p.Arg266Gly Uncertain significance ★ ⚠ same type
OSBP p.Arg376His Uncertain significance ★ ⚠ same type
OSBP p.Arg462Gln 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/osbp-p-pro685arg (accessed [today's date]).

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