Is BICD2 p.Arg12Gln (c.35G>A) pathogenic?

BICD2 p.Arg12Gln (c.35G>A) is classified Uncertain significance in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely benign (0.0911); Absent from gnomAD v4.1; Associated with BICD2-related disorder.

What condition is associated with BICD2 p.Arg12Gln (c.35G>A)?

BICD2 p.Arg12Gln (c.35G>A) is associated with BICD2-related disorder (ClinVar).

How common is BICD2 p.Arg12Gln (c.35G>A) in the general population?

BICD2 p.Arg12Gln (c.35G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICD2 p.Arg12Gln (c.35G>A)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

BICD2 p.Arg12Gln

c.35G>A · rs2537622412 · VCV2629274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BICD2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.05	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 4.4	GERP 0.52, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 42 kb · p 0.00095 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Arg12Gln
Coding: c.35G>A
MANE Select: NM_001003800
dbSNP: rs2537622412
Type: single nucleotide variant
Location: chr9:92764710 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 12: an α-helix

Full BICD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BICD2-related disorder

Similar variants

BICD2 p.Arg12= Likely benign ★ same residue
BICD2 p.Arg160His Uncertain significance ★★ ⚠ same condition
BICD2 p.Arg23Pro Uncertain significance ★★ ⚠ same condition
BICD2 p.Tyr114Ter Pathogenic ★ same condition
BICD2 p.Arg566Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
BICD2 p.His540Arg Uncertain significance ★ ⚠ same condition
BICD2 p.His89Arg Uncertain significance ★ ⚠ same condition
BICD2 p.Ala791Gly 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-arg12gln (accessed [today's date]).

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