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.2265A>T (p.Ala755=)

CA233655

166820 (ClinVar)

Gene: CDKL5 (HGNC:6792)

Condition: CDKL5 disorder (MONDO:0100039)

Inheritance Mode: X-linked inheritance

UUID: ad487149-5605-45f6-b664-92b49a06f2f7

Approved on: 2026-04-23

Published on: 2026-06-26

HGVS expressions

NM_001323289.2:c.2265A>T

NM_001323289.2(CDKL5):c.2265A>T (p.Ala755=)

NC_000023.11:g.18613264A>T

CM000685.2:g.18613264A>T

NC_000023.10:g.18631384A>T

CM000685.1:g.18631384A>T

NC_000023.9:g.18541305A>T

NG_008475.1:g.192660A>T

ENST00000623535.2:c.2265A>T

ENST00000635828.1:c.2265A>T

ENST00000674046.1:c.2265A>T

ENST00000379989.6:c.2265A>T

ENST00000379996.7:c.2265A>T

ENST00000463994.4:c.2265A>T

ENST00000623535.1:c.2265A>T

NM_001037343.1:c.2265A>T

NM_003159.2:c.2265A>T

NM_001323289.1:c.2265A>T

NM_001037343.2:c.2265A>T

NM_003159.3:c.2265A>T

Likely Benign

BP7 BP4 BS2

BS1

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.Ala755= variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2). The silent p.Ala755= variant is not predicted to affect splicing using Splice AI and does not affect a highly conserved nucleotide (BP7, BP4). In summary, the p.Ala755= variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP4, BP7). (CDKL5 Specifications v5.0; curation approved on 4/23/2026)

BP7

The silent p.Ala755= variant is not predicted to affect splicing using Splice AI and does not affect a highly conserved nucleotide (BP7, BP4).

BP4

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

BS2

The p.Ala755= variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2).

BS1

The highest population minor allele frequency of the p.Ala755= variant in CDKL5 in gnomAD v4.1 is 0.000002 in the Non-Finnish European population (not sufficient to meet BS1 criteria).

Curation History

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