IREB2 p.Pro710=
c.2130A>G · VCV4926114
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00305%, nfe)
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 -7.8 | GERP -5.3 |
| Overall | ||
| CADD | 1.099 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00305%
European (non-Finnish) · 36/1,178,846 alleles
Filtering AF
0.00224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00198%
Overall
0.00224%
36/1,609,610 alleles · very rare
exomes 35/1,457,396 · genomes 1/152,214 · joint denominator
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
- IREB2
- Protein
- p.Pro710=
- Coding
- c.2130A>G
- MANE Select
- NM_004136
- Type
- single nucleotide variant
- Location
- chr15:78490475 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.11 · 1 PDB
- Residue 710
- a UniProt-annotated variant site (in ndcama; may drastically decrease protein expression level)
Similar variants
- IREB2 p.Ala534Thr Uncertain significance ★★ ⚠ same type
- IREB2 p.Arg697Trp Uncertain significance ★★ ⚠ same type
- IREB2 p.Asn925Thr Uncertain significance ★★ ⚠ same type
- IREB2 p.Cys53Tyr Uncertain significance ★★ same type
- IREB2 p.Glu917Lys Uncertain significance ★★ ⚠ same type
- IREB2 p.Gly184Asp Uncertain significance ★★ ⚠ same type
- IREB2 p.Gly656Ser Uncertain significance ★★ ⚠ same type
- IREB2 p.His22Leu 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/ireb2-p-pro710 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown