Is CDK5RAP2 p.Asp209fs (c.625dup) pathogenic?

CDK5RAP2 p.Asp209fs (c.625dup) is classified Pathogenic in CDK5RAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-01). Associated with microcephaly 3, primary, autosomal recessive.

What condition is associated with CDK5RAP2 p.Asp209fs (c.625dup)?

CDK5RAP2 p.Asp209fs (c.625dup) is associated with microcephaly 3, primary, autosomal recessive (ClinVar).

CDK5RAP2 p.Asp209fs

c.625dup · VCV3336694

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 7 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.22	GERP -1.4, phastCons 0.001

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

Variant & gene context

Gene: CDK5RAP2
Protein: p.Asp209fs
Coding: c.625dup
MANE Select: NM_018249
Type: Duplication
Location: chr9:120536408 (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.Glu290fs Likely 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-asp209fs (accessed [today's date]).

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