RGR p.Pro250=
c.750C>T · rs748553756 · VCV1097200
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, 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 -9.8 | GERP -13 |
| Overall | ||
| CADD | 0.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00715%
Overall
0.00136%
22/1,614,090 alleles · ultra-rare
exomes 19/1,461,880 · genomes 3/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,028 |
| East Asian | 0.00668% | 14,967 |
| South Asian | 0.00329% | 30,361 |
| African / African-American | 0.00133% | 74,928 |
| European (non-Finnish) | 0.00102% | 98,337 |
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
- RGR
- Protein
- p.Pro250=
- Coding
- c.750C>T
- MANE Select
- NM_001012720
- dbSNP
- rs748553756
- Type
- single nucleotide variant
- Location
- chr10:84258513 (GRCh38)
- Structure
- AlphaFold pLDDT 62.88
- Residue 250
- the ras-gef domain
Similar variants
- RGR p.Pro250Thr Uncertain significance ★ ⚠ same residue
- RGR c.358+1G>A Uncertain significance ★★ same type
- RGR p.Ala110Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala186Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala217Gly Uncertain significance ★★ ⚠ same type
- RGR p.Ala234Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala251Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala251Val 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/rgr-p-pro250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown