Is CDK5RAP2 p.Ala183Pro (c.547G>C) pathogenic?

CDK5RAP2 p.Ala183Pro (c.547G>C) is classified Uncertain significance in CDK5RAP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2013-02-08). AlphaMissense: ambiguous (0.4263); Absent from gnomAD v4.1; Associated with microcephaly 3, primary, autosomal recessive.

What condition is associated with CDK5RAP2 p.Ala183Pro (c.547G>C)?

CDK5RAP2 p.Ala183Pro (c.547G>C) is associated with microcephaly 3, primary, autosomal recessive (ClinVar).

How common is CDK5RAP2 p.Ala183Pro (c.547G>C) in the general population?

CDK5RAP2 p.Ala183Pro (c.547G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK5RAP2 p.Ala183Pro (c.547G>C)?

AlphaMissense predicts ambiguous (score 0.4263) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Ala183Pro

c.547G>C · rs13287734 · VCV21654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4263 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

microcephaly 3, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.4263	ambiguous
REVEL	0.097	moderately benign-leaning
SaProt	LLR -12.65	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.53, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	24.1	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: CDK5RAP2
Protein: p.Ala183Pro
Coding: c.547G>C
MANE Select: NM_018249
dbSNP: rs13287734
Type: single nucleotide variant
Location: chr9:120536487 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.11 · 5 PDB
Residue 183: the 'interaction with nckap5l' region; a UniProt-annotated variant site (in)

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 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
CDK5RAP2 p.Gln1743Ter Pathogenic ★★ same condition
CDK5RAP2 p.Glu1516Ter 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-ala183pro (accessed [today's date]).

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