Is BICD2 p.Asp228Gly (c.683A>G) pathogenic?

BICD2 p.Asp228Gly (c.683A>G) is classified Uncertain significance in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-24). AlphaMissense: likely pathogenic (0.6106); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BICD2 p.Asp228Gly (c.683A>G)?

BICD2 p.Asp228Gly (c.683A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BICD2 p.Asp228Gly (c.683A>G) in the general population?

BICD2 p.Asp228Gly (c.683A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICD2 p.Asp228Gly (c.683A>G)?

AlphaMissense predicts likely pathogenic (score 0.6106) — an in-silico prediction, not a clinical call.

BICD2 p.Asp228Gly

c.683A>G · VCV4840368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6106 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6106	likely pathogenic
REVEL	0.49	indeterminate
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,691 bp · p 0.0012 · regional, not allelic
Overall
CADD	28.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BICD2
Protein: p.Asp228Gly
Coding: c.683A>G
MANE Select: NM_001003800
Type: single nucleotide variant
Location: chr9:92720679 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 228: 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

Similar variants

BICD2 p.Asp228Glu Benign ★ same residue
BICD2 p.Arg694Gly Pathogenic/Likely pathogenic ★★ same condition
BICD2 p.Thr703Met Pathogenic/Likely pathogenic ★★ same condition
BICD2 p.Tyr538Cys Pathogenic ★★ ⚠ same condition
BICD2 c.1062+5G>A Uncertain significance ★★ same condition
BICD2 p.Ala740Ser Uncertain significance ★★ ⚠ same condition
BICD2 p.Arg116Trp Uncertain significance ★★ ⚠ same condition
BICD2 p.Arg160Leu 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-asp228gly (accessed [today's date]).

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