IRF2BP2 p.Pro152=
c.456C>G · rs866756829 · VCV1615465
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00153%, 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 0.71 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 2.292 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00153%
African / African-American · 1/65,560 alleles
Filtering AF
0.000142%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000104%
Overall
0.00046%
6/1,304,214 alleles · very rare
exomes 5/1,153,088 · genomes 1/151,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00153% | 65,560 |
| European (non-Finnish) | 0.000486% | 205,741 |
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.Pro152=
- Coding
- c.456C>G
- MANE Select
- NM_182972
- dbSNP
- rs866756829
- Type
- single nucleotide variant
- Location
- chr1:234609039 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI 0.41 (gnomAD)
- Structure
- AlphaFold pLDDT 56.84 · 3 PDB
- Residue 152
- the 'disordered' region
Similar variants
- IRF2BP2 p.Pro152Leu 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
- IRF2BP2 p.Ala344Val 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-pro152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown