IRF2BPL p.Pro137=
c.411T>G · rs2503078380 · VCV2644405
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00632%, sas)
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 -0.02 | GERP -2.1, phastCons 0.097 |
| Overall | ||
| CADD | 9.177 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00632%
South Asian · 5/79,118 alleles
Filtering AF
0.00245%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00154%
Overall
0.000403%
6/1,489,228 alleles · very rare
exomes 6/1,349,742 · genomes 0/139,486 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00632% | 15,824 |
| East Asian | 0.00285% | 35,144 |
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
- IRF2BPL
- Protein
- p.Pro137=
- Coding
- c.411T>G
- MANE Select
- NM_024496
- dbSNP
- rs2503078380
- Type
- single nucleotide variant
- Location
- chr14:77027382 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.91 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.01 · 1 PDB
- Residue 137
- a UniProt-annotated variant site (in nedamss); a UniProt-annotated variant site (in nedamss; loss of function)
Similar variants
- IRF2BPL p.Arg188Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln117Ter Likely pathogenic ★★ same type
- IRF2BPL p.Gln119Ter Likely pathogenic ★★ same type
- IRF2BPL p.Gln120Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln121Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln122Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln167Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln497Ter Pathogenic/Likely pathogenic ★★ 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/irf2bpl-p-pro137 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown