Is BSCL2 p.Pro182Thr (c.544C>A) pathogenic?

BSCL2 p.Pro182Thr (c.544C>A) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1444); Absent from gnomAD v4.1; Associated with neuronopathy, distal hereditary motor, type 5A.

What condition is associated with BSCL2 p.Pro182Thr (c.544C>A)?

BSCL2 p.Pro182Thr (c.544C>A) is associated with neuronopathy, distal hereditary motor, type 5A, congenital generalized lipodystrophy type 2 (ClinVar).

How common is BSCL2 p.Pro182Thr (c.544C>A) in the general population?

BSCL2 p.Pro182Thr (c.544C>A) is absent from gnomAD v4.1 (gnomAD).

How is Distal hereditary motor neuropathy type 5 inherited?

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

What do computational predictors say about BSCL2 p.Pro182Thr (c.544C>A)?

AlphaMissense predicts likely benign (score 0.1444) — an in-silico prediction, not a clinical call.

BSCL2 p.Pro182Thr

c.544C>A · rs886048442 · VCV305181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1444 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuronopathy, distal hereditary motor, type 5A

Computational evidence

Protein change
AlphaMissense	0.1444	likely benign
REVEL	0.633	indeterminate
SaProt	LLR -11.30	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 2,247 bp · p 9.1e-06 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P118T vs ClinVar P182T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BSCL2
Protein: p.Pro182Thr
Coding: c.544C>A
MANE Select: NM_001122955
dbSNP: rs886048442
Type: single nucleotide variant
Location: chr11:62694654 (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

For Distal hereditary motor neuropathy type 5 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

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
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-pro182thr (accessed [today's date]).

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