RASGRP1 p.Asp487Val
c.1460A>T · rs62621817 · VCV1418149
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9397 | likely pathogenic |
|---|---|---|
| REVEL | 0.706 | pathogenic-leaning |
| SaProt | LLR -14.18 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 0.73 | unconstrained · MANE · 63 kb · p 9.6e-13 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0219% | 4,571 |
| European (non-Finnish)grpmax | 0.0121% | 8,253 |
| Remaining individualsnot grpmax-eligible | 0.00965% | 10,364 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Asp487Val
- Coding
- c.1460A>T
- MANE Select
- NM_005739
- dbSNP
- rs62621817
- Type
- single nucleotide variant
- Location
- chr15:38502390 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.48 (gnomAD)
- Structure
- AlphaFold pLDDT 72.43 · 2 PDB
- Residue 487
- a binding site; 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 ef-hand 1 domain
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-asp487val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown