RIT1 p.Arg91=
c.273G>A · rs2527180518 · VCV2904607
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Noonan syndrome 8
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.38 | GERP -1.1, phastCons 0.99 |
| Overall | ||
| CADD | 9.869 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- RIT1
- Protein
- p.Arg91=
- Coding
- c.273G>A
- MANE Select
- NM_006912
- dbSNP
- rs2527180518
- Type
- single nucleotide variant
- Location
- chr1:155904467 (GRCh38)
- Gene constraint
- LOEUF 0.523 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.78 · 3 PDB
- Residue 91
- an α-helix
Similar variants
- RIT1 p.Arg91Lys Uncertain significance ★ ⚠ same residue
- RIT1 p.Met90Val Pathogenic ★★★ ⚠ same condition
- RIT1 p.Arg123Cys Uncertain significance ★★★ same condition
- RIT1 p.Gly78Glu Uncertain significance ★★★ ⚠ same condition
- RIT1 p.Ala57Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
- RIT1 p.Ala77Gly Pathogenic/Likely pathogenic ★★ same condition
- RIT1 p.Ala77Pro Pathogenic/Likely pathogenic ★★ same condition
- RIT1 p.Ala77Ser Pathogenic/Likely pathogenic ★★ 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/rit1-p-arg91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown