Is CDKL5 p.Phe871Val (c.2611T>G) pathogenic?

CDKL5 p.Phe871Val (c.2611T>G) is classified Uncertain significance in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-31). AlphaMissense: likely benign (0.189); Absent from gnomAD v4.1; Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.Phe871Val (c.2611T>G)?

CDKL5 p.Phe871Val (c.2611T>G) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Phe871Val (c.2611T>G) in the general population?

CDKL5 p.Phe871Val (c.2611T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKL5 p.Phe871Val (c.2611T>G)?

AlphaMissense predicts likely benign (score 0.189) — an in-silico prediction, not a clinical call.

CDKL5 p.Phe871Val

c.2611T>G · rs2147178975 · VCV1446248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.189 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Angelman syndrome-like

Computational evidence

Protein change
AlphaMissense	0.189	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -4.99	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 6.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 30 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKL5
Protein: p.Phe871Val
Coding: c.2611T>G
MANE Select: NM_001323289
dbSNP: rs2147178975
Type: single nucleotide variant
Location: chrX:18628485 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 871: the 'disordered' region; a UniProt-annotated variant site (in dee2); a UniProt-annotated variant site (found in a patient with infatile spasms; likely pathogenic)

Full CDKL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Angelman syndrome-like — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 c.146-1G>A Pathogenic ★★★ same condition
CDKL5 p.Ala157Pro Likely pathogenic ★★★ same condition
CDKL5 p.Ala157Val Likely pathogenic ★★★ same condition
CDKL5 p.Ala40Val Pathogenic ★★★ same condition
CDKL5 p.Arg178Gln Pathogenic ★★★ same condition
CDKL5 p.Arg717= Likely pathogenic ★★★ same condition
CDKL5 p.Arg948Ter Pathogenic ★★★ same condition
CDKL5 p.Asp193Gly Likely pathogenic ★★★ 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/cdkl5-p-phe871val (accessed [today's date]).

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