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.545T>C (p.Leu182Pro)

CA412352546

1700386 (ClinVar)

Gene: CDKL5 (HGNC:6792)

Condition: CDKL5 disorder (MONDO:0100039)

Inheritance Mode: X-linked inheritance

UUID: 6bdfa3c2-2932-40cb-957d-98fa0ae0b77d

Approved on: 2025-08-27

Published on: 2025-09-30

HGVS expressions

NM_001323289.2(CDKL5):c.545T>C (p.Leu182Pro)

NM_001323289.2:c.545T>C

NC_000023.11:g.18584344T>C

CM000685.2:g.18584344T>C

NC_000023.10:g.18602464T>C

CM000685.1:g.18602464T>C

NC_000023.9:g.18512385T>C

NG_008475.1:g.163740T>C

ENST00000623535.2:c.545T>C

ENST00000635828.1:c.545T>C

ENST00000637881.1:c.545T>C

ENST00000674046.1:c.545T>C

ENST00000379989.6:c.545T>C

ENST00000379996.7:c.545T>C

ENST00000463994.4:c.545T>C

ENST00000623535.1:c.545T>C

NM_001037343.1:c.545T>C

NM_003159.2:c.545T>C

NM_001323289.1:c.545T>C

NM_001037343.2:c.545T>C

NM_003159.3:c.545T>C

Likely Pathogenic

PS2 PP3 PM6 PS4_Supporting PM2_Supporting

PS1 PS3 PM1 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 5.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Leu182Pro variant in CDKL5 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with epileptic encephalopathy (PMID 23708187) (PS2). The p.Leu182Pro variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with epileptic encephalopathy (internal database - GeneDx) (PM6). The p.Leu182Pro variant has been observed in at least 2 individuals with epileptic encephalopathy (PMID 23708187, internal database - GeneDx) (PS4_supporting). The p.Leu182Pro 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.Leu182Pro variant in CDKL5 is classified as likely pathogenic for CDKL5 disorder based on the ACMG/AMP criteria (PS2, PS4_supporting, PM6, PM2_Supporting, PP3). (CDKL5 Specifications v.5.0.0; curation approved on 8/27/2025)

PS2

The p.Leu182Pro variant in CDKL5 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with epileptic encephalopathy (PMID 23708187).

PP3

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

PM6

The p.Leu182Pro variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with epileptic encephalopathy (internal database - GeneDx).

PS4_Supporting

The p.Leu182Pro variant has been observed in at least 2 individuals with epileptic encephalopathy (PMID 23708187, internal database - GeneDx).

PM2_Supporting

The p.Leu182Pro variant in CDKL5 is absent from gnomAD v4.1 (PM2_Supporting).

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.