IRF2BP2 p.Pro118=
c.354G>T · rs1430469187 · VCV2957672
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00631%, 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 -6.8 | GERP -1.8 |
| Overall | ||
| CADD | 0.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00631%
African / African-American · 4/63,440 alleles
Filtering AF
0.00207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00129%
Overall
0.000406%
5/1,231,986 alleles · very rare
exomes 1/1,080,792 · genomes 4/151,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00631% | 15,860 |
| Remaining individualsnot grpmax-eligible | 0.00222% | 45,028 |
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.Pro118=
- Coding
- c.354G>T
- MANE Select
- NM_182972
- dbSNP
- rs1430469187
- Type
- single nucleotide variant
- Location
- chr1:234609141 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI 0.41 (gnomAD)
- Structure
- AlphaFold pLDDT 56.84 · 3 PDB
Similar variants
- IRF2BP2 p.Pro118Ser Benign/Likely benign ★★ same residue
- IRF2BP2 p.Pro118Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
- IRF2BP2 p.Pro118Leu 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
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-pro118 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown