IRF2BPL p.Pro596fs
c.1787del · VCV4074734
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
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 | escapes | premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -4.5 | GERP 0.23 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- IRF2BPL
- Protein
- p.Pro596fs
- Coding
- c.1787del
- MANE Select
- NM_024496
- Type
- Deletion
- Location
- chr14:77026006 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.91 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.01 · 1 PDB
- Residue 596
- a UniProt-annotated variant site (in nedamss); a UniProt-annotated variant site (in nedamss; loss of function); the 'disordered' region
Disease context
neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor IRF2BPL-related regressive neurodevelopmental disorder-dystonia-seizures syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Childhood, Infancy, Neonatal
Similar variants
- IRF2BPL p.Ala101fs Likely pathogenic ★★ same condition
- IRF2BPL p.Asn701fs Pathogenic ★★ same condition
- IRF2BPL p.Pro596Ser Uncertain significance ★★ ⚠ same residue
- IRF2BPL p.Gln113fs Benign/Likely benign ★★ same condition
- IRF2BPL p.Gln127del Benign ★★ same condition
- IRF2BPL p.Ala138fs Pathogenic ★ same condition
- IRF2BPL p.Ala159fs Pathogenic ★ same condition
- IRF2BPL p.Ala162fs 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/irf2bpl-p-pro596fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown