IRF3 p.Ser296=
c.888C>T · VCV3861263
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.7 | |
| Overall | ||
| CADD | 5.813 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,922 alleles
Filtering AF
0.0005%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000929%
15/1,613,890 alleles · very rare
exomes 13/1,461,700 · genomes 2/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,461 |
| East Asian | 0.00223% | 44,884 |
| Admixed American | 0.00167% | 60,010 |
| European (non-Finnish) | 0.000932% | 107,271 |
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
- IRF3
- Protein
- p.Ser296=
- Coding
- c.888C>T
- MANE Select
- NM_001571
- Type
- single nucleotide variant
- Location
- chr19:49662042 (GRCh38)
- Gene constraint
- LOEUF 0.949 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.58 · 18 PDB
- Residue 296
- the 'mediates interaction with zdhhc11' region; the 'interaction with herc5' region; a β-strand
Similar variants
- IRF3 p.Arg213Cys Uncertain significance ★★ ⚠ same type
- IRF3 p.Arg96Trp Uncertain significance ★★ ⚠ same type
- IRF3 p.Asn28Lys Uncertain significance ★★ ⚠ same type
- IRF3 p.Asp45Asn Uncertain significance ★★ ⚠ same type
- IRF3 p.Gln15Arg Uncertain significance ★★ ⚠ same type
- IRF3 p.Leu344Phe Uncertain significance ★★ ⚠ same type
- IRF3 p.Ser97Arg Uncertain significance ★★ ⚠ same type
- IRF3 p.Val319Met Uncertain significance ★★ same type
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/irf3-p-ser296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown