IRF3 p.Ser405=
c.1215C>T · rs149842990 · VCV3047399
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.321%, afr)
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 -9.5 | GERP -2.2 |
| Overall | ||
| CADD | 0.483 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.321%
African / African-American · 241/74,992 alleles
Filtering AF
0.288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.275%
Overall
0.0196%
316/1,613,928 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.321% | 311 |
| East Asian | 0.0357% | 2,805 |
| Admixed American | 0.025% | 3,999 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,807 |
| Middle Eastern | 0.0165% | 6,056 |
| South Asian | 0.0165% | 6,072 |
| European (non-Finnish) | 0.00127% | 78,661 |
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.Ser405=
- Coding
- c.1215C>T
- MANE Select
- NM_001571
- dbSNP
- rs149842990
- Type
- single nucleotide variant
- Location
- chr19:49659717 (GRCh38)
- Gene constraint
- LOEUF 0.949 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.58 · 18 PDB
- Residue 405
- an α-helix; the 'mediates interaction with zdhhc11' region
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-ser405 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown