RASGRP1 p.Ser334=
c.1002C>T · rs781469092 · VCV2192932
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0269%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.28 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -2.7, phastCons 1 |
| Overall | ||
| CADD | 12.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0269%
East Asian · 12/44,602 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0122%
Overall
0.00168%
27/1,609,178 alleles · ultra-rare
exomes 22/1,457,130 · genomes 5/152,048 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0269% | 3,717 |
| European (non-Finnish) | 0.00127% | 78,547 |
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.Ser334=
- Coding
- c.1002C>T
- MANE Select
- NM_005739
- dbSNP
- rs781469092
- Type
- single nucleotide variant
- Location
- chr15:38507966 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.48 (gnomAD)
- Structure
- AlphaFold pLDDT 72.43 · 2 PDB
- Residue 334
- the ras-gef domain; 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)
Similar variants
- RASGRP1 p.Ser334del Uncertain significance ★ same residue
- 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
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-ser334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown