Is IRF7 p.Pro250= (c.750C>A) pathogenic?

IRF7 p.Pro250= (c.750C>A) is classified Likely benign in IRF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Very rare (popmax 0.00172%, amr); Associated with immunodeficiency 39.

What condition is associated with IRF7 p.Pro250= (c.750C>A)?

IRF7 p.Pro250= (c.750C>A) is associated with immunodeficiency 39 (ClinVar).

How common is IRF7 p.Pro250= (c.750C>A) in the general population?

IRF7 p.Pro250= (c.750C>A) is very rare (popmax 0.00172%, amr) (gnomAD).

IRF7 p.Pro250=

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.750C>A · rs202066033 · VCV2974537

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

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 0.15
Overall
CADD	1.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00172% Admixed American · 1/57,972 alleles

Overall 6.88e-05% 1/1,454,126 alleles · very rare

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.Pro250=
Coding: c.750C>A
MANE Select: NM_001572
dbSNP: rs202066033
Type: single nucleotide variant
Location: chr11:613967 (GRCh38)
Gene constraint: LOEUF 1.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 1 PDB
Residue 250: 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.Pro250fs 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-pro250 (accessed [today's date]).

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