RRAS p.Pro25=
c.75G>C · rs2122429854 · VCV1647773
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00184%, amr)
Conditions
1
Noonan syndrome
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 0.82 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 14.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00184%
Admixed American · 1/54,276 alleles
Overall
6.43e-05%
1/1,555,050 alleles · very rare
exomes 1/1,403,044 · genomes 0/152,006 · 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
- RRAS
- Protein
- p.Pro25=
- Coding
- c.75G>C
- MANE Select
- NM_006270
- dbSNP
- rs2122429854
- Type
- single nucleotide variant
- Location
- chr19:49640024 (GRCh38)
- Gene constraint
- LOEUF 1.175 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.79 · 2 PDB
- Residue 25
- an α-helix; the 'disordered' region
Similar variants
- RRAS p.Pro25Leu Likely benign ★★ ⚠ same residue
- RRAS p.Ala109Thr Uncertain significance ★★ ⚠ same condition
- RRAS p.Ala162Thr Uncertain significance ★★ ⚠ same condition
- RRAS p.Ala205Val Uncertain significance ★★ ⚠ same condition
- RRAS p.Ala85Val Uncertain significance ★★ ⚠ same condition
- RRAS p.Arg113Gln Uncertain significance ★★ ⚠ same condition
- RRAS p.Arg128Gln Uncertain significance ★★ ⚠ same condition
- RRAS p.Arg132Cys Uncertain significance ★★ same condition
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/rras-p-pro25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown