Is BICD2 p.Ala34Ile (c.100_101delinsAT) pathogenic?

BICD2 p.Ala34Ile (c.100101delinsAT) is classified Uncertain significance in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). Associated with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures.

What condition is associated with BICD2 p.Ala34Ile (c.100_101delinsAT)?

BICD2 p.Ala34Ile (c.100_101delinsAT) is associated with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (ClinVar).

BICD2 p.Ala34Ile

Q: How is Autosomal dominant childhood-onset proximal spinal muscular atrophy inherited?

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

c.100_101delinsAT · VCV3653817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 42 kb · p 0.00095 · regional, not allelic

Variant & gene context

Gene: BICD2
Protein: p.Ala34Ile
Coding: c.100_101delinsAT
MANE Select: NM_001003800
Type: Indel
Location: chr9:92764644 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 34: the 'interacts with dynll1, dync1h1, dync1i2, dctn1 and dctn2' region; an α-helix

Full BICD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant childhood-onset proximal spinal muscular atrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Antenatal, Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

BICD2 p.Ala34= Likely benign ★ same residue
BICD2 p.Phe743Thr Uncertain significance ★ same condition
BICD2 p.Thr123Ile Uncertain significance ★ same condition
BICD2 p.Arg694Cys Pathogenic/Likely pathogenic ★★ same condition
BICD2 p.Lys734Glu Likely pathogenic ★★ same condition
BICD2 p.Ser107Leu Pathogenic ★★ ⚠ same condition
BICD2 p.Thr703Met Pathogenic/Likely pathogenic ★★ same condition
BICD2 p.Tyr556Ser Likely 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/bicd2-p-ala34ile (accessed [today's date]).

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