Is BICD2 p.Gln239His (c.717G>C) pathogenic?

BICD2 p.Gln239His (c.717G>C) is classified Likely benign in BICD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-24). AlphaMissense: ambiguous (0.5308); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with BICD2 p.Gln239His (c.717G>C)?

BICD2 p.Gln239His (c.717G>C) is associated with Inborn genetic diseases, autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (ClinVar).

How common is BICD2 p.Gln239His (c.717G>C) in the general population?

BICD2 p.Gln239His (c.717G>C) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about BICD2 p.Gln239His (c.717G>C)?

AlphaMissense predicts ambiguous (score 0.5308) — an in-silico prediction, not a clinical call.

BICD2 p.Gln239His

c.717G>C · rs751319533 · VCV1757526

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5308 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5308	ambiguous
REVEL	0.271	benign-leaning
SaProt	LLR -8.30	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.39, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,691 bp · p 0.0012 · regional, not allelic
Overall
CADD	24.3	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 0.00667% Admixed American · 4/60,006 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00186% 30/1,614,094 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
European (non-Finnish)	0.0022%	45,386

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.Gln239His
Coding: c.717G>C
MANE Select: NM_001003800
dbSNP: rs751319533
Type: single nucleotide variant
Location: chr9:92720645 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 239: the 'interacts with dynll1, dync1h1, dync1i2, dctn1 and dctn2' 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-gln239his (accessed [today's date]).

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