Is SCP2 p.Pro296Ser (c.886C>T) pathogenic?

SCP2 p.Pro296Ser (c.886C>T) is classified Uncertain significance in SCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-26). AlphaMissense: likely benign (0.2177); Absent from gnomAD v4.1; Associated with sterol carrier protein 2 deficiency.

What condition is associated with SCP2 p.Pro296Ser (c.886C>T)?

SCP2 p.Pro296Ser (c.886C>T) is associated with sterol carrier protein 2 deficiency (ClinVar).

How common is SCP2 p.Pro296Ser (c.886C>T) in the general population?

SCP2 p.Pro296Ser (c.886C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCP2 p.Pro296Ser (c.886C>T)?

AlphaMissense predicts likely benign (score 0.2177) — an in-silico prediction, not a clinical call.

SCP2 p.Pro296Ser

Q: How is Leukoencephalopathy-dystonia-motor neuropathy syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.886C>T · rs1342599570 · VCV977231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

sterol carrier protein 2 deficiency

Computational evidence

Protein change
AlphaMissense	0.2177	likely benign
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -9.58	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 112 kb · p 0.012 · regional, not allelic
Overall
CADD	23.9	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: SCP2
Protein: p.Pro296Ser
Coding: c.886C>T
MANE Select: NM_002979
dbSNP: rs1342599570
Type: single nucleotide variant
Location: chr1:52980456 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.39 · 2 PDB

Full SCP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

sterol carrier protein 2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leukoencephalopathy-dystonia-motor neuropathy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

SCP2 c.825+1G>T Pathogenic/Likely pathogenic ★★ same condition
SCP2 p.Gln371Ter Pathogenic ★★ same condition
SCP2 p.Tyr77Cys Uncertain significance ★★ ⚠ same condition
SCP2 c.973+15T>G Likely benign ★★ same condition
SCP2 c.973+1G>A Likely pathogenic ★ same condition
SCP2 p.His191Arg Uncertain significance ★ ⚠ same condition
SCP2 p.Ser412Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
SCP2 c.588dup Pathogenic/Likely pathogenic ★★ 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/scp2-p-pro296ser (accessed [today's date]).

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