Is IRF2BPL p.Ala92fs (c.273_307del) pathogenic?

IRF2BPL p.Ala92fs (c.273307del) is classified Pathogenic in IRF2BPL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-01). No gnomAD frequency available for this variant; Associated with neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures.

How common is IRF2BPL p.Ala92fs (c.273_307del) in the general population?

IRF2BPL p.Ala92fs (c.273_307del) is no gnomAD frequency available for this variant (gnomAD).

IRF2BPL p.Ala92fs

Q: What condition is associated with IRF2BPL p.Ala92fs (c.273_307del)?

IRF2BPL p.Ala92fs (c.273_307del) is associated with neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (ClinVar).

Q: How is IRF2BPL-related regressive neurodevelopmental disorder-dystonia-seizures syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.273_307del · rs2503079188 · VCV1807567

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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 2	GERP 0.75, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: IRF2BPL
Protein: p.Ala92fs
Coding: c.273_307del
MANE Select: NM_024496
dbSNP: rs2503079188
Type: Deletion
Location: chr14:77027486 (GRCh38)
Gene constraint: LOEUF 0.544 · pLI 0.91 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.01 · 1 PDB

Full IRF2BPL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 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.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
IRF2BPL p.Ala94fs 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-ala92fs (accessed [today's date]).

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