ROBO2 p.Arg99=
c.297C>A · rs1029843225 · VCV1957257
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 0.23 | GERP -1.3, phastCons 0.6 |
| Overall | ||
| CADD | 6.744 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,000 alleles
Overall
0.000248%
4/1,614,028 alleles · very rare
exomes 2/1,461,894 · genomes 2/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,000 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| African / African-American | 0.00134% | 74,900 |
| European (non-Finnish) | 8.47e-05% | 1,180,054 |
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
- ROBO2
- Protein
- p.Arg99=
- Coding
- c.297C>A
- MANE Select
- NM_001395656
- dbSNP
- rs1029843225
- Type
- single nucleotide variant
- Location
- chr3:77098249 (GRCh38)
- Gene constraint
- LOEUF 0.412 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.78 · 6 PDB
- Residue 99
- the ig-like c2-type 1 domain
Similar variants
- ROBO2 c.1244-1G>A Uncertain significance ★★ same type
- ROBO2 c.3148+2T>C Uncertain significance ★★ same type
- ROBO2 p.Ala112Gly Uncertain significance ★★ same type
- ROBO2 p.Ala1211Gly Uncertain significance ★★ ⚠ same type
- ROBO2 p.Ala124= Uncertain significance ★★ same type
- ROBO2 p.Ala124Val Uncertain significance ★★ same type
- ROBO2 p.Ala556Thr Uncertain significance ★★ ⚠ same type
- ROBO2 p.Ala824Val 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/robo2-p-arg99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown