Is IRF7 p.Leu289fs (c.864_865dup) pathogenic?

IRF7 p.Leu289fs (c.864865dup) is classified Uncertain significance in IRF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). No gnomAD frequency available for this variant; Associated with immunodeficiency 39.

What condition is associated with IRF7 p.Leu289fs (c.864_865dup)?

IRF7 p.Leu289fs (c.864_865dup) is associated with immunodeficiency 39 (ClinVar).

How common is IRF7 p.Leu289fs (c.864_865dup) in the general population?

IRF7 p.Leu289fs (c.864_865dup) is no gnomAD frequency available for this variant (gnomAD).

IRF7 p.Leu289fs

Q: How is Predisposition to severe viral infection due to IRF7 deficiency inherited?

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

c.864_865dup · rs2493903965 · VCV2867825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

immunodeficiency 39

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1

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: IRF7
Protein: p.Leu289fs
Coding: c.864_865dup
MANE Select: NM_001572
dbSNP: rs2493903965
Type: Microsatellite
Location: chr11:613577 (GRCh38)
Gene constraint: LOEUF 1.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 1 PDB
Residue 289: a UniProt-annotated variant site (abolishes ifnb induction upon sendai virus infection); the 'necessary for the interaction with nmi' region

Full IRF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 39 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Predisposition to severe viral infection due to IRF7 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

IRF7 c.848-45_848-16del Benign/Likely benign ★★ same condition
IRF7 c.1238-5_1238-3del Uncertain significance ★ same condition
IRF7 c.21-21_21-20del Uncertain significance ★ same condition
IRF7 c.395-10TC[3] Uncertain significance ★ same condition
IRF7 c.766+6_766+7del Uncertain significance ★ same condition
IRF7 c.848-75CTGTCCCCGCCCACCCCCGTCACTCACAGC[3] Uncertain significance ★ same condition
IRF7 c.848-7CA[2] Uncertain significance ★ same condition
IRF7 p.Ala164fs Uncertain significance ★ 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/irf7-p-leu289fs (accessed [today's date]).

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