Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001323289.2(CDKL5):c.89G>A (p.Cys30Tyr)

CA412489863

487576 (ClinVar)

Gene: CDKL5 (HGNC:6792)

Condition: CDKL5 disorder (MONDO:0100039)

Inheritance Mode: X-linked inheritance

UUID: 91a503ff-78ef-4eff-989d-4bf3e262f782

Approved on: 2026-08-24

Published on: 2026-09-24

HGVS expressions

NM_001323289.2(CDKL5):c.89G>A (p.Cys30Tyr)

NM_001323289.2:c.89G>A

NC_000023.11:g.18510844G>A

CM000685.2:g.18510844G>A

NC_000023.10:g.18528964G>A

CM000685.1:g.18528964G>A

NC_000023.9:g.18438885G>A

NG_008475.1:g.90240G>A

ENST00000623535.2:c.89G>A

ENST00000635828.1:c.89G>A

ENST00000637881.1:c.89G>A

ENST00000674046.1:c.89G>A

ENST00000379989.6:c.89G>A

ENST00000379996.7:c.89G>A

ENST00000463994.4:c.89G>A

ENST00000623364.3:c.89G>A

ENST00000623535.1:c.89G>A

ENST00000624700.3:c.89G>A

NM_001037343.1:c.89G>A

NM_003159.2:c.89G>A

NM_001323289.1:c.89G>A

NM_001037343.2:c.89G>A

NM_003159.3:c.89G>A

Likely Pathogenic

PM2_Supporting PP3 PM1 PM6 PS4_Supporting

BS3 BS1 BP4 PS1 PS3 BA1 PM5

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDKL5 Version 6.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Cys30Tyr variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with developmental and epileptic encephalopathy (PMID 35701389) (PM6). The p.Cys30Tyr variant has been observed in at least 1 additional individual with clinical features of CDKL5 disorder (internal database - Labcorp (formerly Invitae)) (PS4_Supporting). The p.Cys30Tyr variant occurs in the well-characterized ATP binding region of the CDKL5 gene (PMID: 17993579, 23064044, 28544139, 29264392) (PM1). The p.Cys30Tyr variant in CDKL5 is absent from gnomAD v4.1 (PM2_Supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Cys30Tyr variant in CDKL5 is classified as Likely Pathogenic for CDKL5 disorder based on the ACMG/AMP criteria (PM1, PM6, PS4_Supporting, PM2_Supporting, PP3). (CDKL5 Specifications v6.0; curation approved on 8/24/2026)

PM2_Supporting

The p.Cys30Tyr variant in CDKL5 is absent from gnomAD v4.1 (PM2_Supporting).

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).

PM1

The p.Cys30Tyr variant occurs in the well-characterized ATP binding region of the CDKL5 gene (PMID: 17993579, 23064044, 28544139, 29264392) (PM1).

PM6

The p.Cys30Tyr variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with developmental and epileptic encephalopathy (PMID 35701389) (PM6).

PS4_Supporting

The p.Cys30Tyr variant has been observed in at least 1 additional individual with clinical features of CDKL5 disorder (internal database - Invitae) (PS4_Supporting).

BS3