Is CDK5RAP2 p.Glu290fs (c.866_867dup) pathogenic?

CDK5RAP2 p.Glu290fs (c.866867dup) is classified Likely pathogenic in CDK5RAP2 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.0011%, sas); Associated with microcephaly 3, primary, autosomal recessive.

What condition is associated with CDK5RAP2 p.Glu290fs (c.866_867dup)?

CDK5RAP2 p.Glu290fs (c.866_867dup) is associated with microcephaly 3, primary, autosomal recessive (ClinVar).

How common is CDK5RAP2 p.Glu290fs (c.866_867dup) in the general population?

CDK5RAP2 p.Glu290fs (c.866_867dup) is very rare (popmax 0.0011%, sas) (gnomAD).

CDK5RAP2 p.Glu290fs

c.866_867dup · rs2539627558 · VCV3235013

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

microcephaly 3, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,862 alleles

Overall 6.88e-05% 1/1,452,930 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: CDK5RAP2
Protein: p.Glu290fs
Coding: c.866_867dup
MANE Select: NM_018249
dbSNP: rs2539627558
Type: Duplication
Location: chr9:120528755 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.11 · 5 PDB

Full CDK5RAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly 3, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK5RAP2 p.Ala1627fs Likely pathogenic ★ same condition
CDK5RAP2 p.Asp209fs Pathogenic same condition
CDK5RAP2 c.4005-1G>A Pathogenic ★★ same condition
CDK5RAP2 c.4963+1G>A Likely pathogenic ★★ same condition
CDK5RAP2 p.Arg1403Ter Pathogenic/Likely pathogenic ★★ same condition
CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same condition
CDK5RAP2 p.Arg1558Ter Pathogenic ★★ same condition
CDK5RAP2 p.Arg427Ter Pathogenic ★★ 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/cdk5rap2-p-glu290fs (accessed [today's date]).

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