Is BICD2 p.Gly596Val (c.1787G>T) pathogenic?

BICD2 p.Gly596Val (c.1787G>T) is classified Uncertain significance in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-12). AlphaMissense: likely benign (0.0845); Very rare (popmax 6.89e-05%); Associated with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures.

How common is BICD2 p.Gly596Val (c.1787G>T) in the general population?

BICD2 p.Gly596Val (c.1787G>T) is very rare (popmax 6.89e-05%) (gnomAD).

What do computational predictors say about BICD2 p.Gly596Val (c.1787G>T)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

BICD2 p.Gly596Val

Q: What condition is associated with BICD2 p.Gly596Val (c.1787G>T)?

BICD2 p.Gly596Val (c.1787G>T) 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.1787G>T · rs1377173037 · VCV653344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.89e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.29, phastCons 0.95
Regional constraint	o/e 0.72	unconstrained · MANE · 3,839 bp · p 5.4e-09 · regional, not allelic
Overall
CADD	19.84	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.89e-05%

Overall 6.89e-05% 1/1,451,490 alleles · very rare

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: BICD2
Protein: p.Gly596Val
Coding: c.1787G>T
MANE Select: NM_001003800
dbSNP: rs1377173037
Type: single nucleotide variant
Location: chr9:92718858 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 596: the 'interaction with kif5a' region; the 'disordered' region; the 'interaction with ranbp2' 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.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
BICD2 c.1062+5G>A Uncertain significance ★★ same condition
BICD2 p.Ala326Pro Uncertain significance ★★ ⚠ same condition
BICD2 p.Ala595Val 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-gly596val (accessed [today's date]).

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