Is BSCL2 p.Pro367= (c.1101G>A) pathogenic?

BSCL2 p.Pro367= (c.1101G>A) is classified Conflicting classifications of pathogenicity in BSCL2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-23). Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with BSCL2 p.Pro367= (c.1101G>A)?

BSCL2 p.Pro367= (c.1101G>A) is associated with Inborn genetic diseases, severe neurodegenerative syndrome with lipodystrophy, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Pro367= (c.1101G>A) in the general population?

BSCL2 p.Pro367= (c.1101G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

BSCL2 p.Pro367=

c.1101G>A · rs746737457 · VCV543290

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.246	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -4.2, phastCons 0.14
Overall
CADD	12.95	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 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00136% 22/1,613,548 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.0111%	8,980
Admixed American	0.00333%	29,999
Finnishnot grpmax-eligible	0.00157%	63,522
African / African-American	0.00133%	74,942
South Asian	0.0011%	91,072
European (non-Finnish)	0.000932%	107,275

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.Pro367=
Coding: c.1101G>A
MANE Select: NM_001122955
dbSNP: rs746737457
Type: single nucleotide variant
Location: chr11:62690839 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB
Residue 367: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe neurodegenerative syndrome with lipodystrophy Charcot-Marie-Tooth disease type 2

Similar variants

BSCL2 p.Pro367Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BSCL2 p.Pro367Ser Uncertain significance ★ ⚠ same residue
BSCL2 c.1006-2A>C 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 p.Ala276Pro Pathogenic ★★ same condition
BSCL2 p.Arg329Ter Pathogenic ★★ same condition
BSCL2 p.Arg339Ter 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-pro367 (accessed [today's date]).

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