RASGRP1 p.Ser314=
c.942G>A · VCV3721058
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss, 24 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -4.7 |
| Overall | ||
| CADD | 1.174 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,990 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00174%
28/1,613,276 alleles · ultra-rare
exomes 25/1,461,094 · genomes 3/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 5,999 |
| East Asian | 0.00223% | 44,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,422 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
| European (non-Finnish) | 0.00119% | 84,246 |
| South Asian | 0.0011% | 91,078 |
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.Ser314=
- Coding
- c.942G>A
- MANE Select
- NM_005739
- Type
- single nucleotide variant
- Location
- chr15:38511628 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.48 (gnomAD)
- Structure
- AlphaFold pLDDT 72.43 · 2 PDB
- Residue 314
- 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 p.Ser314Leu 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-ser314 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown