Is IRF8 p.Arg296= (c.888C>T) pathogenic?

IRF8 p.Arg296= (c.888C>T) is classified Likely benign in IRF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). Very rare (popmax 0.00668%, eas); Associated with immunodeficiency 32B.

What condition is associated with IRF8 p.Arg296= (c.888C>T)?

IRF8 p.Arg296= (c.888C>T) is associated with immunodeficiency 32B, Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency (ClinVar).

How common is IRF8 p.Arg296= (c.888C>T) in the general population?

IRF8 p.Arg296= (c.888C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

How is Chronic Epstein-Barr virus infection syndrome inherited?

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

IRF8 p.Arg296=

c.888C>T · rs757802318 · VCV2079109

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

immunodeficiency 32B

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 -7.4	GERP -4.9
Overall
CADD	6.219	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,898 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00205% 33/1,612,286 alleles · very rare exomes 31/1,459,996 · genomes 2/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,966
South Asian	0.00549%	18,214
Remaining individualsnot grpmax-eligible	0.0048%	20,822
European (non-Finnish)	0.00178%	56,190
Admixed American	0.00167%	59,996

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: IRF8
Protein: p.Arg296=
Coding: c.888C>T
MANE Select: NM_002163
dbSNP: rs757802318
Type: single nucleotide variant
Location: chr16:85918703 (GRCh38)
Gene constraint: LOEUF 0.462 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.54

Full IRF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 32B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency

For Chronic Epstein-Barr virus infection syndrome (Orphanet):

Inheritance: Unknown
Onset: Adolescent, Adult, Childhood

Similar variants

IRF8 p.Arg296Cys Uncertain significance ★★ ⚠ same residue
IRF8 p.Arg296His Uncertain significance ★ ⚠ same residue
IRF8 p.Arg140His Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg228Cys Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg268Trp Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg315His Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg340Trp Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg361Gly 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/irf8-p-arg296 (accessed [today's date]).

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