RIT1 p.Phe82=
c.246T>C · VCV3664045
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.039 | GERP -3, phastCons 0.075 |
| Overall | ||
| CADD | 9.404 | 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.Phe82=
- Coding
- c.246T>C
- MANE Select
- NM_006912
- Type
- single nucleotide variant
- Location
- chr1:155904494 (GRCh38)
- Gene constraint
- LOEUF 0.523 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.78 · 3 PDB
- Residue 82
- a UniProt-annotated variant site (in ns8; results in increased elk1 transcriptional activation; abolishes interaction with lztr1); a UniProt-annotated variant site (found in patients with features of noonan syndrome; likely pathogenic)
Similar variants
- RIT1 p.Phe82Cys Pathogenic ★★ same residue
- RIT1 p.Phe82Ile Pathogenic ★★ same residue
- RIT1 p.Phe82Leu Pathogenic/Likely pathogenic ★★ same residue
- RIT1 p.Phe82Val Pathogenic ★★ same residue
- RIT1 p.Phe82Ser Pathogenic ★ same residue
- RIT1 p.Met90Val Pathogenic ★★★ ⚠ same condition
- RIT1 p.Arg123Cys Uncertain significance ★★★ same condition
- RIT1 p.Gly78Glu 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/rit1-p-phe82 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown