RASGRP2 p.Lys333=
c.999G>A · rs374345558 · VCV2047727
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0442%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 0.82, phastCons 1 |
| Overall | ||
| CADD | 10.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0442%
European (non-Finnish) · 521/1,180,026 alleles
Filtering AF
0.041%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0398%
Overall
0.0341%
550/1,613,478 alleles · ultra-rare
exomes 517/1,461,208 · genomes 33/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0442% | 2,265 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,469 |
| Admixed American | 0.00833% | 12,000 |
| African / African-American | 0.00801% | 12,492 |
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.Lys333=
- Coding
- c.999G>A
- MANE Select
- NM_001098671
- dbSNP
- rs374345558
- Type
- single nucleotide variant
- Location
- chr11:64736849 (GRCh38)
- Gene constraint
- LOEUF 0.854 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.48 · 2 PDB
- Residue 333
- the ras-gef domain; a UniProt-annotated variant site (in bdplt18); a UniProt-annotated variant site (in bdplt18; lack of mutant protein in platelets from a patient homozygous for the mutation); an α-helix
Similar variants
- RASGRP2 p.Lys333Asn Likely pathogenic ★ same residue
- 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
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-lys333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown