Is BICD2 p.Glu252Lys (c.754G>A) pathogenic?

BICD2 p.Glu252Lys (c.754G>A) is classified Uncertain significance in BICD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-13). AlphaMissense: likely pathogenic (0.8563); Very rare (popmax 0.0022%, sas).

How common is BICD2 p.Glu252Lys (c.754G>A) in the general population?

BICD2 p.Glu252Lys (c.754G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BICD2 p.Glu252Lys (c.754G>A)?

AlphaMissense predicts likely pathogenic (score 0.8563) — an in-silico prediction, not a clinical call.

BICD2 p.Glu252Lys

c.754G>A · rs776953074 · VCV617992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8563 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8563	likely pathogenic
REVEL	0.538	indeterminate
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,691 bp · p 0.0012 · regional, not allelic
Overall
CADD	31.0	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 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00041% 6/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
European (non-Finnish)	0.000339%	295,008

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.Glu252Lys
Coding: c.754G>A
MANE Select: NM_001003800
dbSNP: rs776953074
Type: single nucleotide variant
Location: chr9:92720608 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.89 · 2 PDB
Residue 252: the 'interacts with dynll1, dync1h1, dync1i2, dctn1 and dctn2' region

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

Similar variants

BICD2 p.Glu252= 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
BICD2 p.Thr703Met Pathogenic/Likely 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-glu252lys (accessed [today's date]).

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