Is IRF7 p.Pro115fs (c.344del) pathogenic?

IRF7 p.Pro115fs (c.344del) is classified Uncertain significance in IRF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-02). Associated with immunodeficiency 39.

What condition is associated with IRF7 p.Pro115fs (c.344del)?

IRF7 p.Pro115fs (c.344del) is associated with immunodeficiency 39 (ClinVar).

IRF7 p.Pro115fs

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.344del · VCV3729592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1

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

Variant & gene context

Gene: IRF7
Protein: p.Pro115fs
Coding: c.344del
MANE Select: NM_001572
Type: Deletion
Location: chr11:614847 (GRCh38)
Gene constraint: LOEUF 1.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 1 PDB
Residue 115: a DNA-binding 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 p.Pro115Leu Uncertain significance ★ ⚠ same residue
IRF7 p.Asn94fs Uncertain significance ★★ same condition
IRF7 p.Gly247fs Uncertain significance ★★ same condition
IRF7 c.1357-75_1357-14del Likely benign ★★ same condition
IRF7 c.848-77_848-18del Likely benign ★★ same condition
IRF7 c.21-33del Uncertain significance ★ same condition
IRF7 c.394+26_469del Uncertain significance ★ same condition
IRF7 c.395-10_395-8del 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-pro115fs (accessed [today's date]).

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