RASGRP2 p.Pro33=
c.99G>A · rs569640858 · VCV2722628
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0239%, amr)
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 -1.2 | GERP -3.5 |
| Overall | ||
| CADD | 9.555 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0239%
Admixed American · 14/58,664 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0115%
Overall
0.00604%
97/1,604,720 alleles · ultra-rare
exomes 85/1,452,506 · genomes 12/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0239% | 4,190 |
| Remaining individualsnot grpmax-eligible | 0.0113% | 8,872 |
| European (non-Finnish) | 0.00629% | 15,886 |
| African / African-American | 0.00134% | 74,888 |
| South Asian | 0.00112% | 89,558 |
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
- RASGRP2
- Protein
- p.Pro33=
- Coding
- c.99G>A
- MANE Select
- NM_001098671
- dbSNP
- rs569640858
- Type
- single nucleotide variant
- Location
- chr11:64742087 (GRCh38)
- Gene constraint
- LOEUF 0.854 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.48 · 2 PDB
- Residue 33
- the n-terminal ras-gef domain; an α-helix
Similar variants
- RASGRP2 p.Gly305Asp Likely pathogenic ★★ same type
- RASGRP2 p.Arg387Gly Uncertain significance ★★ ⚠ same type
- RASGRP2 p.Arg593His Uncertain significance ★★ ⚠ same type
- RASGRP2 p.Asn330Lys Uncertain significance ★★ ⚠ same type
- RASGRP2 p.Gly331Arg Uncertain significance ★★ ⚠ same type
- RASGRP2 p.Gly492Trp Uncertain significance ★★ ⚠ same type
- RASGRP2 p.Leu107Ile Uncertain significance ★★ ⚠ same type
- RASGRP2 p.Lys55Met 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/rasgrp2-p-pro33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown