Is BSCL2 p.Ser311= (c.933C>T) pathogenic?

BSCL2 p.Ser311= (c.933C>T) is classified Likely benign in BSCL2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-22). Ultra-rare (popmax 0.0111%, eas); Associated with severe neurodegenerative syndrome with lipodystrophy.

What condition is associated with BSCL2 p.Ser311= (c.933C>T)?

BSCL2 p.Ser311= (c.933C>T) is associated with severe neurodegenerative syndrome with lipodystrophy, congenital generalized lipodystrophy type 2, hereditary spastic paraplegia 17 (ClinVar).

How common is BSCL2 p.Ser311= (c.933C>T) in the general population?

BSCL2 p.Ser311= (c.933C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

BSCL2 p.Ser311=

Q: How is Progressive encephalopathy-severe neurodegeneration-lipodystrophy syndrome inherited?

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

c.933C>T · rs748195771 · VCV1647630

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

severe neurodegenerative syndrome with lipodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1	GERP -4.6
Overall
CADD	12.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,882 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000958% 14/1,461,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,976
South Asian	0.0011%	91,074
European (non-Finnish)	0.000678%	147,504

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BSCL2
Protein: p.Ser311=
Coding: c.933C>T
dbSNP: rs748195771
Type: single nucleotide variant
Location: chr11:62691352 (GRCh38)

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

Disease context

severe neurodegenerative syndrome with lipodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital generalized lipodystrophy type 2 hereditary spastic paraplegia 17 Charcot-Marie-Tooth disease type 2 neuronopathy, distal hereditary motor, type 5C

For Progressive encephalopathy-severe neurodegeneration-lipodystrophy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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-ser311 (accessed [today's date]).

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