Is BSCL2 p.Ser128fs (c.384_385delinsGGA) pathogenic?

BSCL2 p.Ser128fs (c.384385delinsGGA) is classified Conflicting classifications of pathogenicity in BSCL2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2017-05-05). Absent from gnomAD; Associated with Berardinelli-Seip congenital lipodystrophy.

What condition is associated with BSCL2 p.Ser128fs (c.384_385delinsGGA)?

BSCL2 p.Ser128fs (c.384_385delinsGGA) is associated with Berardinelli-Seip congenital lipodystrophy, congenital generalized lipodystrophy type 2 (ClinVar).

How common is BSCL2 p.Ser128fs (c.384_385delinsGGA) in the general population?

BSCL2 p.Ser128fs (c.384_385delinsGGA) 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.Ser128fs

c.384_385delinsGGA · rs786205068 · VCV4531

Conflicting classifications of pathogenicity No assertion criteria

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Berardinelli-Seip congenital lipodystrophy

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 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 2.3, 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.Ser128fs
Coding: c.384_385delinsGGA
MANE Select: NM_001122955
dbSNP: rs786205068
Type: Indel
Location: chr11:62705320 (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

Berardinelli-Seip congenital lipodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital generalized lipodystrophy type 2

For Congenital generalized lipodystrophy (Orphanet):

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

Similar variants

BSCL2 p.Arg90Ser Uncertain significance ★ 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
BSCL2 p.Ala276Pro Pathogenic ★★ same condition
BSCL2 p.Ala282fs 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-ser128fs (accessed [today's date]).

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