IRF2BP2 p.Pro104=
c.312C>T · rs766398538 · VCV1592989
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.17%, 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 0.063 | GERP -0.2, phastCons 0.88 |
| Overall | ||
| CADD | 10.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.17%
African / African-American · 109/64,050 alleles
Filtering AF
0.144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.135%
Overall
0.00977%
126/1,289,076 alleles · rare
exomes 42/1,137,860 · genomes 84/151,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.17% | 588 |
| Admixed American | 0.0383% | 2,614 |
| Middle Eastern | 0.0298% | 3,354 |
| Remaining individualsnot grpmax-eligible | 0.0126% | 7,962 |
| European (non-Finnish) | 9.78e-05% | 1,022,498 |
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
- IRF2BP2
- Protein
- p.Pro104=
- Coding
- c.312C>T
- MANE Select
- NM_182972
- dbSNP
- rs766398538
- Type
- single nucleotide variant
- Location
- chr1:234609183 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI 0.41 (gnomAD)
- Structure
- AlphaFold pLDDT 56.84 · 3 PDB
Similar variants
- IRF2BP2 p.Pro104Leu Uncertain significance ★ ⚠ same residue
- IRF2BP2 p.Pro104Ser Uncertain significance ★ ⚠ same residue
- IRF2BP2 p.Ala143Gly Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala209Gly Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala214Thr Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala246Val Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala254Thr Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala276Thr 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/irf2bp2-p-pro104 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown