Is BSCL2 p.Ser205= (c.615C>T) pathogenic?

BSCL2 p.Ser205= (c.615C>T) is classified Conflicting classifications of pathogenicity in BSCL2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-07-31). Ultra-rare (popmax 0.0733%, afr); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Ser205= (c.615C>T)?

BSCL2 p.Ser205= (c.615C>T) is associated with Charcot-Marie-Tooth disease type 2, congenital generalized lipodystrophy type 2, neuronopathy, distal hereditary motor, type 5A (ClinVar).

How common is BSCL2 p.Ser205= (c.615C>T) in the general population?

BSCL2 p.Ser205= (c.615C>T) is ultra-rare (popmax 0.0733%, afr) (gnomAD).

BSCL2 p.Ser205=

c.615C>T · rs140208002 · VCV305180

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0733%, afr)

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP -3.9, phastCons 0.87
Overall
CADD	5.297	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0733% African / African-American · 55/75,008 alleles

Filtering AF 0.0578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0522%

Overall 0.00446% 72/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0733%	1,364
Admixed American	0.0133%	7,499
Remaining individualsnot grpmax-eligible	0.008%	12,502
South Asian	0.0022%	45,539
European (non-Finnish)	0.000169%	590,005

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.Ser205=
Coding: c.615C>T
MANE Select: NM_001122955
dbSNP: rs140208002
Type: single nucleotide variant
Location: chr11:62694583 (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

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

Also linked: congenital generalized lipodystrophy type 2 neuronopathy, distal hereditary motor, type 5A

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-ser205 (accessed [today's date]).

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