Is BSCL2 p.Thr366Ala (c.1096A>G) pathogenic?

BSCL2 p.Thr366Ala (c.1096A>G) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-05). AlphaMissense: likely benign (0.0598); Very rare (popmax 0.00223%, eas); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Thr366Ala (c.1096A>G)?

BSCL2 p.Thr366Ala (c.1096A>G) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Thr366Ala (c.1096A>G) in the general population?

BSCL2 p.Thr366Ala (c.1096A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BSCL2 p.Thr366Ala (c.1096A>G)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

BSCL2 p.Thr366Ala

c.1096A>G · rs776379711 · VCV845115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.72	GERP -4.5
Regional constraint	o/e 1.03	unconstrained · MANE · 2,047 bp · p 0.6 · regional, not allelic
Overall
CADD	8.635	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T302A vs ClinVar T366A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,868 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000753% 11/1,461,330 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,868
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.000763%	131,110

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.Thr366Ala
Coding: c.1096A>G
dbSNP: rs776379711
Type: single nucleotide variant
Location: chr11:62690844 (GRCh38)

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

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-thr366ala (accessed [today's date]).

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