Is BICD2 p.Ala735fs (c.2203del) pathogenic?

BICD2 p.Ala735fs (c.2203del) is classified Uncertain significance in BICD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-29). Associated with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures.

BICD2 p.Ala735fs

Q: What condition is associated with BICD2 p.Ala735fs (c.2203del)?

BICD2 p.Ala735fs (c.2203del) is associated with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (ClinVar).

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.2203del · VCV4537710

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BICD2
Protein: p.Ala735fs
Coding: c.2203del
MANE Select: NM_001003800
Type: Deletion
Location: chr9:92717852 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 735: an α-helix; the 'interaction with ranbp2' region; the 'interacts with rab6a' region

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.Lys734del Likely pathogenic ★ same condition
BICD2 c.2258+757_2305del Uncertain significance ★ same condition
BICD2 p.Ala402_Gln407del Uncertain significance ★ same condition
BICD2 p.Arg578fs Uncertain significance ★ same condition
BICD2 p.Asn412del Uncertain significance ★ same condition
BICD2 p.Glu559_Arg566del Uncertain significance ★ same condition
BICD2 p.Gly570_Pro575del Uncertain significance ★ same condition
BICD2 p.Lys504del Uncertain significance ★ 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-ala735fs (accessed [today's date]).

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