Is BICD2 p.Thr376= (c.1128G>A) pathogenic?

BICD2 p.Thr376= (c.1128G>A) is classified Likely benign in BICD2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0267%, amr); Associated with Inborn genetic diseases.

What condition is associated with BICD2 p.Thr376= (c.1128G>A)?

BICD2 p.Thr376= (c.1128G>A) is associated with Inborn genetic diseases, autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (ClinVar).

How common is BICD2 p.Thr376= (c.1128G>A) in the general population?

BICD2 p.Thr376= (c.1128G>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

BICD2 p.Thr376=

c.1128G>A · rs184715042 · VCV385928

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 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 -15	GERP -4.4
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,020 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00205% 33/1,613,526 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,751
East Asian	0.00668%	14,959
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
South Asian	0.0033%	30,349
African / African-American	0.00133%	75,074
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: BICD2
Protein: p.Thr376=
Coding: c.1128G>A
MANE Select: NM_001003800
dbSNP: rs184715042
Type: single nucleotide variant
Location: chr9:92719517 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 376: the 'interacts with dynll1, dync1h1, dync1i2, dctn1 and dctn2' region; the 'interaction with kif5a' 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.Thr376Met Conflicting classifications of pathogenicity ★ ⚠ same residue
BICD2 p.Thr376Ala Likely benign ★ same residue
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

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-thr376 (accessed [today's date]).

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