ROBO3 p.Val522=
c.1566G>A · rs762190285 · VCV764999
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0826%, mid)
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 6.7 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 8.706 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0826%
Middle Eastern · 5/6,056 alleles
Filtering AF
0.0325%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00496%
80/1,612,070 alleles · ultra-rare
exomes 72/1,459,750 · genomes 8/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0826% | 1,211 |
| South Asian | 0.0299% | 3,345 |
| Admixed American | 0.0151% | 6,642 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,485 |
| European (non-Finnish) | 0.00288% | 34,685 |
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
- ROBO3
- Protein
- p.Val522=
- Coding
- c.1566G>A
- MANE Select
- NM_022370
- dbSNP
- rs762190285
- Type
- single nucleotide variant
- Location
- chr11:124873339 (GRCh38)
- Gene constraint
- LOEUF 0.749 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.99 · 3 PDB
- Residue 522
- the ig-like c2-type 5 domain
Similar variants
- ROBO3 p.Val522Leu Uncertain significance ★ same residue
- ROBO3 p.Val522Met Uncertain significance ★ same residue
- ROBO3 c.767-1G>A Pathogenic/Likely pathogenic ★★ same type
- ROBO3 p.Arg245Trp Likely pathogenic ★★ same type
- ROBO3 p.Arg703Pro Likely pathogenic ★★ same type
- ROBO3 p.Ile95Thr Likely pathogenic ★★ same type
- ROBO3 p.Pro771Leu Likely pathogenic ★★ ⚠ same type
- ROBO3 c.*67C>T 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/robo3-p-val522 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown