Is BICD2 p.Pro549Leu (c.1646C>T) pathogenic?

BICD2 p.Pro549Leu (c.1646C>T) is classified Likely pathogenic in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-01). AlphaMissense: likely pathogenic (0.9959); Absent from gnomAD v4.1.

How common is BICD2 p.Pro549Leu (c.1646C>T) in the general population?

BICD2 p.Pro549Leu (c.1646C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICD2 p.Pro549Leu (c.1646C>T)?

AlphaMissense predicts likely pathogenic (score 0.9959) — an in-silico prediction, not a clinical call.

BICD2 p.Pro549Leu

c.1646C>T · rs1064795764 · VCV422412

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9959 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9959	likely pathogenic ✓ concordant with ClinVar · top 4% in BICD2
REVEL	0.624	indeterminate
SaProt	LLR -15.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 55 bp · p 0.0001 · regional, not allelic
Overall
CADD	29.9	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.Pro549Leu
Coding: c.1646C>T
MANE Select: NM_001003800
dbSNP: rs1064795764
Type: single nucleotide variant
Location: chr9:92718999 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 549: the 'interaction with kif5a' region

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

Similar variants

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
BICD2 p.Thr703Met Pathogenic/Likely pathogenic ★★ same type
BICD2 p.Tyr538Cys 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-pro549leu (accessed [today's date]).

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