Is BICD2 p.Glu62Ala (c.185A>C) pathogenic?

BICD2 p.Glu62Ala (c.185A>C) is classified Uncertain significance in BICD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-14). AlphaMissense: likely benign (0.2634); Very rare (popmax 0.00417%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BICD2 p.Glu62Ala (c.185A>C)?

BICD2 p.Glu62Ala (c.185A>C) is associated with Inborn genetic diseases, autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (ClinVar).

How common is BICD2 p.Glu62Ala (c.185A>C) in the general population?

BICD2 p.Glu62Ala (c.185A>C) is very rare (popmax 0.00417%, nfe) (gnomAD).

What do computational predictors say about BICD2 p.Glu62Ala (c.185A>C)?

AlphaMissense predicts likely benign (score 0.2634) — an in-silico prediction, not a clinical call.

BICD2 p.Glu62Ala

c.185A>C · rs935505713 · VCV838404

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00417%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2634	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -9.30	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 7.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 42 kb · p 0.00095 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.00417% European (non-Finnish) · 48/1,150,148 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00309% 48/1,554,450 alleles · very rare

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.Glu62Ala
Coding: c.185A>C
MANE Select: NM_001003800
dbSNP: rs935505713
Type: single nucleotide variant
Location: chr9:92764560 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 62: the 'interacts with dynll1, dync1h1, dync1i2, dctn1 and dctn2' region; an α-helix

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-glu62ala (accessed [today's date]).

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