Is IRF7 p.Pro269= (c.807G>A) pathogenic?

IRF7 p.Pro269= (c.807G>A) is classified Likely benign in IRF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-19). Very rare (popmax 0.00691%, nfe); Associated with immunodeficiency 39.

What condition is associated with IRF7 p.Pro269= (c.807G>A)?

IRF7 p.Pro269= (c.807G>A) is associated with immunodeficiency 39 (ClinVar).

How common is IRF7 p.Pro269= (c.807G>A) in the general population?

IRF7 p.Pro269= (c.807G>A) is very rare (popmax 0.00691%, nfe) (gnomAD).

IRF7 p.Pro269=

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.807G>A · rs375273132 · VCV764721

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00691%, nfe)

Conditions

immunodeficiency 39

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1
Overall
CADD	2.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00691% European (non-Finnish) · 81/1,171,468 alleles

Filtering AF 0.00567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00518%

Overall 0.00567% 90/1,586,844 alleles · very rare exomes 82/1,434,768 · genomes 8/152,076 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00691%	14,463
African / African-American	0.00543%	18,417
Finnishnot grpmax-eligible	0.005%	19,985
East Asian	0.00226%	44,334
Remaining individualsnot grpmax-eligible	0.00163%	61,316

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IRF7
Protein: p.Pro269=
Coding: c.807G>A
MANE Select: NM_001572
dbSNP: rs375273132
Type: single nucleotide variant
Location: chr11:613825 (GRCh38)
Gene constraint: LOEUF 1.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 1 PDB
Residue 269: a UniProt-annotated variant site (abolishes ifnb induction upon sendai virus infection); the 'disordered' 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.Pro269Leu Uncertain significance ★ ⚠ same residue
IRF7 c.20+39G>C Uncertain significance ★★ same condition
IRF7 c.21-16G>A Uncertain significance ★★ same condition
IRF7 c.21-19C>T Uncertain significance ★★ same condition
IRF7 c.848-1G>C Uncertain significance ★★ same condition
IRF7 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
IRF7 p.Ala251Pro Uncertain significance ★★ ⚠ same condition
IRF7 p.Ala258Val 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-pro269 (accessed [today's date]).

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