Is BICD2 p.Arg501Trp (c.1501C>T) pathogenic?

BICD2 p.Arg501Trp (c.1501C>T) is classified Conflicting classifications of pathogenicity in BICD2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1404); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with BICD2 p.Arg501Trp (c.1501C>T)?

BICD2 p.Arg501Trp (c.1501C>T) is associated with Inborn genetic diseases, autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (ClinVar).

How common is BICD2 p.Arg501Trp (c.1501C>T) in the general population?

BICD2 p.Arg501Trp (c.1501C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about BICD2 p.Arg501Trp (c.1501C>T)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

BICD2 p.Arg501Trp

c.1501C>T · rs373224610 · VCV846210

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,691 bp · p 0.0012 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,928 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00385% 62/1,611,946 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,488
European (non-Finnish)	0.00432%	23,137
East Asian	0.00223%	44,890
South Asian	0.0022%	45,544
Finnishnot grpmax-eligible	0.00161%	61,994
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Arg501Trp
Coding: c.1501C>T
MANE Select: NM_001003800
dbSNP: rs373224610
Type: single nucleotide variant
Location: chr9:92719144 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 501: a UniProt-annotated variant site (in smaled2a; the mutation causes increased interaction with dynein; the mutant protein accumulates abnormally in the perinuclear region where it forms ring-like structures that colocalize with rab6a); 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.Arg501Gln Uncertain significance ★★ ⚠ same residue
BICD2 p.Arg501Gly Uncertain significance ★ ⚠ same residue
BICD2 p.Arg501= Likely benign ★ same residue
BICD2 p.Arg501Pro Conflicting classifications of pathogenicity ⚠ 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

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-arg501trp (accessed [today's date]).

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