RASGRP1 p.Phe690Ser
c.2069T>C · rs763001228 · VCV1524874
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0881 | likely benign |
|---|---|---|
| REVEL | 0.257 | benign-leaning |
| SaProt | LLR -3.86 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP 1, phastCons 0.98 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 8,350 bp · p 0.023 · regional, not allelic |
| Overall | ||
| CADD | 15.98 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0508% | 1,967 |
| Remaining individualsnot grpmax-eligible | 0.00496% | 20,177 |
| European (non-Finnish) | 0.00121% | 82,650 |
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
- RASGRP1
- Protein
- p.Phe690Ser
- Coding
- c.2069T>C
- MANE Select
- NM_005739
- dbSNP
- rs763001228
- Type
- single nucleotide variant
- Location
- chr15:38494572 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.48 (gnomAD)
- Structure
- AlphaFold pLDDT 72.43 · 2 PDB
- Residue 690
- a UniProt-annotated variant site (in imd64; loss of protein expression); a UniProt-annotated variant site (in imd64); a UniProt-annotated variant site (in imd64; no effect on protein expression; decreased t cell activation); the 'disordered' region; the 'suppress the pt region-mediated translocation to plasma membrane' region
Similar variants
- RASGRP1 c.327-1C>G Pathogenic/Likely pathogenic ★★ same type
- RASGRP1 p.Arg81Ter Pathogenic/Likely pathogenic ★★ same type
- RASGRP1 p.Ala57Ser Uncertain significance ★★ ⚠ same type
- RASGRP1 p.Arg167Cys Uncertain significance ★★ ⚠ same type
- RASGRP1 p.Arg177His Uncertain significance ★★ ⚠ same type
- RASGRP1 p.Arg663Gln Uncertain significance ★★ ⚠ same type
- RASGRP1 p.Arg741His Uncertain significance ★★ ⚠ same type
- RASGRP1 p.Asn241Ser 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/rasgrp1-p-phe690ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown