Is KDM5A p.Pro17fs (c.50del) pathogenic?

KDM5A p.Pro17fs (c.50del) is classified Likely pathogenic in KDM5A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). Associated with El Hayek-Chahrour neurodevelopmental disorder.

What condition is associated with KDM5A p.Pro17fs (c.50del)?

KDM5A p.Pro17fs (c.50del) is associated with El Hayek-Chahrour neurodevelopmental disorder (ClinVar).

KDM5A p.Pro17fs

c.50del · VCV4531407

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

El Hayek-Chahrour neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.6	GERP -5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: KDM5A
Protein: p.Pro17fs
Coding: c.50del
MANE Select: NM_001042603
Type: Deletion
Location: chr12:389042 (GRCh38)
Gene constraint: LOEUF 0.27 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.98 · 46 PDB
Residue 17: an α-helix

Full KDM5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

El Hayek-Chahrour neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM5A c.166-6_169del Likely pathogenic ★ same condition
KDM5A c.672+1488_1149+711del Pathogenic same condition
KDM5A c.4074+1G>A Likely pathogenic ★★ same condition
KDM5A p.Ile1011Thr Uncertain significance ★★ ⚠ same condition
KDM5A p.Gln832Ter Pathogenic ★ same condition
KDM5A p.Arg1350Ter Conflicting classifications of pathogenicity ★ same condition
KDM5A p.Gln576Ter Uncertain significance ★ same condition
KDM5A c.2541+1G>T 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/kdm5a-p-pro17fs (accessed [today's date]).

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