Is OSBPL3 p.Phe73Ser (c.218T>C) pathogenic?

OSBPL3 p.Phe73Ser (c.218T>C) is classified Uncertain significance in OSBPL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely pathogenic (0.9682); Absent from gnomAD v4.1.

How common is OSBPL3 p.Phe73Ser (c.218T>C) in the general population?

OSBPL3 p.Phe73Ser (c.218T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OSBPL3 p.Phe73Ser (c.218T>C)?

AlphaMissense predicts likely pathogenic (score 0.9682) — an in-silico prediction, not a clinical call.

OSBPL3 p.Phe73Ser

c.218T>C · rs2536729257 · VCV3207058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9682 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9682	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	LLR -14.59	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 27 kb · p 0.69 · regional, not allelic
Overall
CADD	25.5	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: OSBPL3
Protein: p.Phe73Ser
Coding: c.218T>C
MANE Select: NM_015550
dbSNP: rs2536729257
Type: single nucleotide variant
Location: chr7:24871791 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.93 · 3 PDB
Residue 73: the ph domain

Full OSBPL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OSBPL3 p.Ala254Thr Uncertain significance ★ ⚠ same type
OSBPL3 p.Ala350Val Uncertain significance ★ ⚠ same type
OSBPL3 p.Ala412Thr Uncertain significance ★ ⚠ same type
OSBPL3 p.Ala414Thr Uncertain significance ★ ⚠ same type
OSBPL3 p.Ala508Ser Uncertain significance ★ ⚠ same type
OSBPL3 p.Ala508Thr Uncertain significance ★ ⚠ same type
OSBPL3 p.Ala508Val Uncertain significance ★ ⚠ same type
OSBPL3 p.Ala592Val 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/osbpl3-p-phe73ser (accessed [today's date]).

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