Is BICD2 p.Ala704= (c.2112C>T) pathogenic?

BICD2 p.Ala704= (c.2112C>T) is classified Likely benign in BICD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-19). Ultra-rare (popmax 0.0267%, amr); Associated with Inborn genetic diseases.

What condition is associated with BICD2 p.Ala704= (c.2112C>T)?

BICD2 p.Ala704= (c.2112C>T) is associated with Inborn genetic diseases, autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (ClinVar).

How common is BICD2 p.Ala704= (c.2112C>T) in the general population?

BICD2 p.Ala704= (c.2112C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

BICD2 p.Ala704=

c.2112C>T · rs767670894 · VCV474271

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -5.1
Overall
CADD	0.773	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/59,900 alleles

Filtering AF 0.0168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00391% 63/1,612,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,744
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,387
European (non-Finnish)	0.00331%	30,251
Remaining individualsnot grpmax-eligible	0.0032%	31,205
East Asian	0.00223%	44,888
African / African-American	0.00134%	74,878

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.Ala704=
Coding: c.2112C>T
MANE Select: NM_001003800
dbSNP: rs767670894
Type: single nucleotide variant
Location: chr9:92717943 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 704: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Similar variants

BICD2 p.Arg694Cys Pathogenic/Likely pathogenic ★★ same condition
BICD2 p.Arg694Gly 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.Tyr538Cys Pathogenic ★★ ⚠ same condition
BICD2 p.Tyr556Ser Likely pathogenic ★★ ⚠ same condition
BICD2 c.1062+5G>A 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-ala704 (accessed [today's date]).

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