IREB2 p.Val596=
c.1788A>G · rs112039230 · VCV2194266
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0822%, 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 0.32 | GERP -4.7, phastCons 0.7 |
| Overall | ||
| CADD | 4.665 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0822%
African / African-American · 61/74,214 alleles
Filtering AF
0.0656%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0597%
Overall
0.00463%
73/1,577,184 alleles · ultra-rare
exomes 37/1,424,944 · genomes 36/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0822% | 1,217 |
| Middle Eastern | 0.0166% | 6,014 |
| Remaining individualsnot grpmax-eligible | 0.00979% | 10,217 |
| Admixed American | 0.00503% | 19,881 |
| South Asian | 0.00111% | 89,800 |
| European (non-Finnish) | 8.72e-05% | 1,147,276 |
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.Val596=
- Coding
- c.1788A>G
- MANE Select
- NM_004136
- dbSNP
- rs112039230
- Type
- single nucleotide variant
- Location
- chr15:78487811 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.11 · 1 PDB
- Residue 596
- 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-val596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown