Is BICD2 p.Phe530Ser (c.1589T>C) pathogenic?

BICD2 p.Phe530Ser (c.1589T>C) is classified Likely pathogenic in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-03-24). AlphaMissense: likely pathogenic (0.9786); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BICD2 p.Phe530Ser (c.1589T>C)?

BICD2 p.Phe530Ser (c.1589T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BICD2 p.Phe530Ser (c.1589T>C) in the general population?

BICD2 p.Phe530Ser (c.1589T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICD2 p.Phe530Ser (c.1589T>C)?

AlphaMissense predicts likely pathogenic (score 0.9786) — an in-silico prediction, not a clinical call.

BICD2 p.Phe530Ser

c.1589T>C · rs797044920 · VCV208737

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9786 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9786	likely pathogenic ✓ concordant with ClinVar · top 9% in BICD2
REVEL	0.49	indeterminate
SaProt	LLR -11.50	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 9.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,691 bp · p 0.0012 · regional, not allelic
Overall
CADD	29.4	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.Phe530Ser
Coding: c.1589T>C
MANE Select: NM_001003800
dbSNP: rs797044920
Type: single nucleotide variant
Location: chr9:92719056 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 530: the 'interaction with kif5a' 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.Phe530Leu Uncertain significance ★ ⚠ 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-phe530ser (accessed [today's date]).

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