Is BICD2 p.Ala326Val (c.977C>T) pathogenic?

BICD2 p.Ala326Val (c.977C>T) is classified Benign in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-02). AlphaMissense: likely benign (0.0624); Very rare (popmax 0.000169%, nfe).

How common is BICD2 p.Ala326Val (c.977C>T) in the general population?

BICD2 p.Ala326Val (c.977C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about BICD2 p.Ala326Val (c.977C>T)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

BICD2 p.Ala326Val

c.977C>T · rs1175583344 · VCV736113

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.87	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 3	GERP -1.8, phastCons 0.19
Regional constraint	o/e 0.84	unconstrained · MANE · 1,691 bp · p 0.0012 · regional, not allelic
Overall
CADD	5.934	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 0.000169% European (non-Finnish) · 2/1,180,024 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,790 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.Ala326Val
Coding: c.977C>T
MANE Select: NM_001003800
dbSNP: rs1175583344
Type: single nucleotide variant
Location: chr9:92720385 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 326: the 'interacts with dynll1, dync1h1, dync1i2, dctn1 and dctn2' region; the 'disordered' region

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

Similar variants

BICD2 p.Ala326Pro Uncertain significance ★★ ⚠ same residue
BICD2 p.Ala326Ser Likely benign ★ same residue
BICD2 p.Arg694Cys Pathogenic/Likely pathogenic ★★ same type
BICD2 p.Arg694Gly Pathogenic/Likely pathogenic ★★ same type
BICD2 p.Arg694His Pathogenic/Likely pathogenic ★★ same type
BICD2 p.Glu774Lys Pathogenic/Likely pathogenic ★★ same type
BICD2 p.Lys734Glu Likely pathogenic ★★ same type
BICD2 p.Ser107Leu Pathogenic ★★ ⚠ same type

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-ala326val (accessed [today's date]).

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