RASGRP1 p.Ala296=
c.888T>C · rs1357947394 · VCV2812307
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
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 -0.47 | GERP -4.1 |
| Overall | ||
| CADD | 10.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,664 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.00131%
2/152,194 alleles · very 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
- RASGRP1
- Protein
- p.Ala296=
- Coding
- c.888T>C
- MANE Select
- NM_005739
- dbSNP
- rs1357947394
- Type
- single nucleotide variant
- Location
- chr15:38511682 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.48 (gnomAD)
- Structure
- AlphaFold pLDDT 72.43 · 2 PDB
- Residue 296
- the ras-gef domain; a UniProt-annotated variant site (in imd64; loss of protein expression); a UniProt-annotated variant site (in imd64); an α-helix
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-ala296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown