Is BSCL2 p.Ser208= (c.624G>A) pathogenic?

BSCL2 p.Ser208= (c.624G>A) is classified Likely benign in BSCL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-29). Ultra-rare (popmax 0.0682%, afr); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Ser208= (c.624G>A)?

BSCL2 p.Ser208= (c.624G>A) is associated with Charcot-Marie-Tooth disease type 2, congenital generalized lipodystrophy type 2, hereditary spastic paraplegia 17 (ClinVar).

How common is BSCL2 p.Ser208= (c.624G>A) in the general population?

BSCL2 p.Ser208= (c.624G>A) is ultra-rare (popmax 0.0682%, afr) (gnomAD).

BSCL2 p.Ser208=

c.624G>A · rs138532996 · VCV697875

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0682%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -4.2
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0682% African / African-American · 51/74,822 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.00428% 69/1,613,802 alleles · ultra-rare exomes 35/1,461,870 · genomes 34/151,932 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0682%	1,467
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Admixed American	0.00334%	29,979
European (non-Finnish)	0.000763%	131,111

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.Ser208=
Coding: c.624G>A
MANE Select: NM_001122955
dbSNP: rs138532996
Type: single nucleotide variant
Location: chr11:62694574 (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 hereditary spastic paraplegia 17 severe neurodegenerative syndrome with lipodystrophy 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-ser208 (accessed [today's date]).

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