Is BSCL2 p.Cys196= (c.588C>T) pathogenic?

BSCL2 p.Cys196= (c.588C>T) is classified Conflicting classifications of pathogenicity in BSCL2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0164%, mid); Associated with neuronopathy, distal hereditary motor, type 5A.

What condition is associated with BSCL2 p.Cys196= (c.588C>T)?

BSCL2 p.Cys196= (c.588C>T) is associated with neuronopathy, distal hereditary motor, type 5A, congenital generalized lipodystrophy type 2, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Cys196= (c.588C>T) in the general population?

BSCL2 p.Cys196= (c.588C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Distal hereditary motor neuropathy type 5 inherited?

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

BSCL2 p.Cys196=

c.588C>T · rs369806785 · VCV220467

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

neuronopathy, distal hereditary motor, type 5A

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 2.9	GERP -1.1, phastCons 1
Overall
CADD	10.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0128% 207/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.0163%	6,146
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Finnishnot grpmax-eligible	0.00781%	12,805
Admixed American	0.00333%	29,990
South Asian	0.0011%	91,090

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.Cys196=
Coding: c.588C>T
MANE Select: NM_001122955
dbSNP: rs369806785
Type: single nucleotide variant
Location: chr11:62694610 (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

neuronopathy, distal hereditary motor, type 5A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital generalized lipodystrophy type 2 Charcot-Marie-Tooth disease type 2 hereditary spastic paraplegia

For Distal hereditary motor neuropathy type 5 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

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-cys196 (accessed [today's date]).

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