RRAS p.Val33=
c.99G>A · VCV3712082
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, eas)
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 5.8 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 16.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
East Asian · 7/42,270 alleles
Filtering AF
0.00776%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.000489%
7/1,432,388 alleles · ultra-rare
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.Val33=
- Coding
- c.99G>A
- MANE Select
- NM_006270
- Type
- single nucleotide variant
- Location
- chr19:49640000 (GRCh38)
- Gene constraint
- LOEUF 1.175 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.79 · 2 PDB
- Residue 33
- a β-strand
Similar variants
- RRAS p.Val33Ala Uncertain significance ★ ⚠ 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-val33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown