Is BICD2 p.Val485Phe (c.1453G>T) pathogenic?

BICD2 p.Val485Phe (c.1453G>T) is classified Benign/Likely benign in BICD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-19). AlphaMissense: likely benign (0.1695); Ultra-rare (popmax 0.0306%, afr); Associated with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures.

How common is BICD2 p.Val485Phe (c.1453G>T) in the general population?

BICD2 p.Val485Phe (c.1453G>T) is ultra-rare (popmax 0.0306%, afr) (gnomAD).

What do computational predictors say about BICD2 p.Val485Phe (c.1453G>T)?

AlphaMissense predicts likely benign (score 0.1695) — an in-silico prediction, not a clinical call.

BICD2 p.Val485Phe

Q: What condition is associated with BICD2 p.Val485Phe (c.1453G>T)?

BICD2 p.Val485Phe (c.1453G>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.1453G>T · rs199519253 · VCV578487

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1695 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0306%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Computational evidence

Protein change
AlphaMissense	0.1695	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -9.15	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 1.2	GERP -2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,691 bp · p 0.0012 · regional, not allelic
Overall
CADD	20.2	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 0.0306% African / African-American · 23/75,050 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.00161% 26/1,610,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0306%	3,263
East Asian	0.00446%	22,440
European (non-Finnish)	8.47e-05%	1,179,972

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.Val485Phe
Coding: c.1453G>T
MANE Select: NM_001003800
dbSNP: rs199519253
Type: single nucleotide variant
Location: chr9:92719192 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 485: the 'interaction with kif5a' 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-val485phe (accessed [today's date]).

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