Is OSBPL2 p.Ser20Phe (c.59C>T) pathogenic?

OSBPL2 p.Ser20Phe (c.59C>T) is classified Uncertain significance in OSBPL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). AlphaMissense: likely benign (0.1077); Absent from gnomAD v4.1.

How common is OSBPL2 p.Ser20Phe (c.59C>T) in the general population?

OSBPL2 p.Ser20Phe (c.59C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OSBPL2 p.Ser20Phe (c.59C>T)?

AlphaMissense predicts likely benign (score 0.1077) — an in-silico prediction, not a clinical call.

OSBPL2 p.Ser20Phe

c.59C>T · VCV3600862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1077 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1077	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.36, phastCons 0.93
Regional constraint	o/e 1.07	unconstrained · MANE · 7,438 bp · p 0.55 · regional, not allelic
Overall
CADD	21.6	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: OSBPL2
Protein: p.Ser20Phe
Coding: c.59C>T
MANE Select: NM_144498
Type: single nucleotide variant
Location: chr20:62260002 (GRCh38)
Gene constraint: LOEUF 0.467 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 83.92 · 1 PDB
Residue 20: the 'disordered' region; a modified residue (phosphoserine)

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

Similar variants

OSBPL2 p.Ser20Pro 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-ser20phe (accessed [today's date]).

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