Is BSCL2 p.Arg171fs (c.512_519del) pathogenic?

BSCL2 p.Arg171fs (c.512519del) is classified Likely pathogenic in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). Associated with hereditary spastic paraplegia 17.

What condition is associated with BSCL2 p.Arg171fs (c.512_519del)?

BSCL2 p.Arg171fs (c.512_519del) 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.Arg171fs

c.512_519del · VCV3599931

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -3.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BSCL2
Protein: p.Arg171fs
Coding: c.512_519del
MANE Select: NM_001122955
Type: Deletion
Location: chr11:62694679 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB

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.Ala282fs Pathogenic/Likely pathogenic ★★ same condition
BSCL2 p.Arg454fs Pathogenic/Likely pathogenic ★★ same condition
BSCL2 p.Tyr277fs Pathogenic ★★ same condition
BSCL2 p.Arg171Cys Uncertain significance ★★ ⚠ same residue
BSCL2 p.Arg171His Uncertain significance ★★ ⚠ same residue
BSCL2 p.Arg171Leu Uncertain significance ★★ ⚠ same residue
BSCL2 p.Gly325fs Likely pathogenic ★ same condition
BSCL2 p.Glu424fs Uncertain significance ★ 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-arg171fs (accessed [today's date]).

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