RASGRP2 p.Pro405=
c.1215G>A · rs758747785 · VCV2641929
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.30 | gain · loss 0.05 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.6 |
| Overall | ||
| CADD | 2.142 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,076 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00174%
28/1,613,702 alleles · ultra-rare
exomes 25/1,461,542 · genomes 3/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,076 |
| African / African-American | 0.00401% | 24,968 |
| European (non-Finnish) | 0.00195% | 51,300 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,460 |
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.Pro405=
- Coding
- c.1215G>A
- MANE Select
- NM_001098671
- dbSNP
- rs758747785
- Type
- single nucleotide variant
- Location
- chr11:64735623 (GRCh38)
- Gene constraint
- LOEUF 0.854 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.48 · 2 PDB
- Residue 405
- 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); the 'disordered' region
Similar variants
- RASGRP2 p.Pro405Leu Uncertain significance ★ ⚠ 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-pro405 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown