Is BSCL2 p.Arg288fs (c.862dup) pathogenic?

BSCL2 p.Arg288fs (c.862dup) is classified Likely pathogenic in BSCL2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-26). Absent from gnomAD; Associated with congenital generalized lipodystrophy type 2.

What condition is associated with BSCL2 p.Arg288fs (c.862dup)?

BSCL2 p.Arg288fs (c.862dup) is associated with congenital generalized lipodystrophy type 2 (ClinVar).

How common is BSCL2 p.Arg288fs (c.862dup) in the general population?

BSCL2 p.Arg288fs (c.862dup) is absent from gnomAD (gnomAD).

How is Congenital generalized lipodystrophy inherited?

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

BSCL2 p.Arg288fs

c.862dup · rs2134695130 · VCV1687147

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital generalized lipodystrophy type 2

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 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BSCL2
Protein: p.Arg288fs
Coding: c.862dup
MANE Select: NM_001122955
dbSNP: rs2134695130
Type: Duplication
Location: chr11:62692376 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB
Residue 288: the 'disordered' region

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

Disease context

congenital generalized lipodystrophy type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital generalized lipodystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

BSCL2 p.Arg288= Conflicting classifications of pathogenicity ★ same residue
BSCL2 p.Ala276fs Likely pathogenic ★★ same condition
BSCL2 p.Ile326fs Pathogenic ★★ same condition
BSCL2 p.Leu315fs Pathogenic ★★ same condition
BSCL2 p.Thr173fs Pathogenic ★★ same condition
BSCL2 p.Tyr117fs Uncertain significance same condition
BSCL2 c.1006-2A>G Pathogenic/Likely pathogenic ★★ same condition
BSCL2 c.486+1G>A 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/bscl2-p-arg288fs (accessed [today's date]).

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