Is CDK5RAP2 p.Lys828Glu (c.2482A>G) pathogenic?

CDK5RAP2 p.Lys828Glu (c.2482A>G) is classified Conflicting classifications of pathogenicity in CDK5RAP2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-09-30). AlphaMissense: likely benign (0.0852); Rare (popmax 0.148%, mid).

How common is CDK5RAP2 p.Lys828Glu (c.2482A>G) in the general population?

CDK5RAP2 p.Lys828Glu (c.2482A>G) is rare (popmax 0.148%, mid) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Lys828Glu (c.2482A>G)?

AlphaMissense predicts likely benign (score 0.0852) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Lys828Glu

c.2482A>G · rs549081765 · VCV432919

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0852 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0852	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -5.38	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 0.054	GERP -4.8, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	0.235	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 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00929% 150/1,614,228 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
South Asian	0.056%	1,786
Admixed American	0.0366%	2,729
Remaining individualsnot grpmax-eligible	0.0144%	6,946
African / African-American	0.00933%	10,722
European (non-Finnish)	0.00441%	22,693

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.Lys828Glu
Coding: c.2482A>G
MANE Select: NM_018249
dbSNP: rs549081765
Type: single nucleotide variant
Location: chr9:120453767 (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

Similar variants

CDK5RAP2 p.Lys828= Conflicting classifications of pathogenicity ★ same residue
CDK5RAP2 c.4005-1G>A Pathogenic ★★ same type
CDK5RAP2 c.4963+1G>A Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1403Ter Pathogenic/Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1558Ter Pathogenic ★★ same type
CDK5RAP2 p.Arg427Ter Pathogenic ★★ same type
CDK5RAP2 p.Gln1301Ter 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/cdk5rap2-p-lys828glu (accessed [today's date]).

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