Is BSCL2 p.Arg90Ser (c.270_271delinsTT) pathogenic?

BSCL2 p.Arg90Ser (c.270271delinsTT) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). Associated with hereditary spastic paraplegia 17.

What condition is associated with BSCL2 p.Arg90Ser (c.270_271delinsTT)?

BSCL2 p.Arg90Ser (c.270_271delinsTT) is associated with hereditary spastic paraplegia 17, congenital generalized lipodystrophy type 2, severe neurodegenerative syndrome with lipodystrophy (ClinVar).

How is Autosomal dominant spastic paraplegia type 17 inherited?

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

BSCL2 p.Arg90Ser

c.270_271delinsTT · VCV3599934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

hereditary spastic paraplegia 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.65 · regional, not allelic

Variant & gene context

Gene: BSCL2
Protein: p.Arg90Ser
Coding: c.270_271delinsTT
MANE Select: NM_001122955
Type: Indel
Location: chr11:62705434 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB
Residue 90: a UniProt-annotated variant site (in spg17 and hmnd13; also found in patients with hereditary motor and sensory neuropathy type 2; does not affect the function in lipid storage)

Full BSCL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital generalized lipodystrophy type 2 severe neurodegenerative syndrome with lipodystrophy neuronopathy, distal hereditary motor, type 5C

For Autosomal dominant spastic paraplegia type 17 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

BSCL2 p.Arg90Trp Uncertain significance ★ ⚠ same residue
BSCL2 p.Arg90= Likely benign ★ same residue
BSCL2 p.Ser128fs Conflicting classifications of pathogenicity same condition
BSCL2 c.1006-2A>G Pathogenic/Likely pathogenic ★★ same condition
BSCL2 c.486+1G>A Pathogenic/Likely pathogenic ★★ same condition
BSCL2 c.631-1G>C Pathogenic/Likely pathogenic ★★ same condition
BSCL2 c.766-2A>G Pathogenic ★★ same condition
BSCL2 p.Ala276fs 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/bscl2-p-arg90ser (accessed [today's date]).

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