Is CDK5RAP2 p.Glu243Lys (c.727G>A) pathogenic?

CDK5RAP2 p.Glu243Lys (c.727G>A) is classified Likely benign in CDK5RAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.1319); Very rare (popmax 0.00167%, amr); Associated with intellectual disability.

What condition is associated with CDK5RAP2 p.Glu243Lys (c.727G>A)?

CDK5RAP2 p.Glu243Lys (c.727G>A) is associated with intellectual disability (ClinVar).

How common is CDK5RAP2 p.Glu243Lys (c.727G>A) in the general population?

CDK5RAP2 p.Glu243Lys (c.727G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Glu243Lys (c.727G>A)?

AlphaMissense predicts likely benign (score 0.1319) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Glu243Lys

c.727G>A · rs138588916 · VCV975517

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1319 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.1319	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.95, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	22.3	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 0.00167% Admixed American · 1/59,996 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,613,852 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,996
European (non-Finnish)	0.00161%	62,101

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.Glu243Lys
Coding: c.727G>A
MANE Select: NM_018249
dbSNP: rs138588916
Type: single nucleotide variant
Location: chr9:120530076 (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

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK5RAP2 p.Glu243Ter Pathogenic ★ same residue
CDK5RAP2 p.Ala762Thr Uncertain significance ★ ⚠ same condition
CDK5RAP2 p.Arg260Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
CDK5RAP2 p.Arg427Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
CDK5RAP2 p.Asn497Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
CDK5RAP2 c.5308-4G>C Likely benign same condition
CDK5RAP2 p.Glu49Lys Likely benign same condition
CDK5RAP2 p.Ser1782Asn Likely benign ⚠ 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-glu243lys (accessed [today's date]).

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