Is BSCL2 p.Glu379= (c.1137A>G) pathogenic?

BSCL2 p.Glu379= (c.1137A>G) is classified Benign in BSCL2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 22.9%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Glu379= (c.1137A>G)?

BSCL2 p.Glu379= (c.1137A>G) is associated with Charcot-Marie-Tooth disease type 2, lipodystrophy, congenital generalized lipodystrophy type 2 (ClinVar).

BSCL2 p.Glu379=

Q: How common is BSCL2 p.Glu379= (c.1137A>G) in the general population?

BSCL2 p.Glu379= (c.1137A>G) is common (popmax 22.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1137A>G · rs6856 · VCV128533

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 22.9%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.201	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.74	GERP -4.2
Overall
CADD	5.574	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.9% European (non-Finnish) · 270,594/1,179,768 alleles

Filtering AF 22.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.8%

Overall 20.6% 332,627/1,613,344 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	22.9%	4
Amishnot grpmax-eligible	19.6%	5
Remaining individualsnot grpmax-eligible	18.7%	5
Middle Eastern	17.4%	6
South Asian	16.9%	6
Ashkenazi Jewishnot grpmax-eligible	16%	6
Admixed American	13.7%	7
Finnishnot grpmax-eligible	13.6%	7
African / African-American	10.2%	10
East Asian	10.1%	10

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.Glu379=
Coding: c.1137A>G
MANE Select: NM_001122955
dbSNP: rs6856
Type: single nucleotide variant
Location: chr11:62690803 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB
Residue 379: the 'disordered' region

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

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lipodystrophy congenital generalized lipodystrophy type 2 hereditary spastic paraplegia 17 severe neurodegenerative syndrome with lipodystrophy neuronopathy, distal hereditary motor, type 5A hereditary spastic paraplegia neuronopathy, distal hereditary motor, type 5C

Similar variants

BSCL2 c.1006-2A>C Likely pathogenic ★★ 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.Ala276Pro Pathogenic ★★ same condition
BSCL2 p.Arg202Ter Pathogenic ★★ same condition
BSCL2 p.Arg329Ter 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-glu379 (accessed [today's date]).

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