RUNX1 p.Arg271=
c.813G>A · rs763723245 · VCV1155123
ClinGen expert panel — Myeloid Malignancy VCEP
Likely Benign for hereditary thrombocytopenia and hematologic cancer predisposition syndrome. Applied ACMG criteria (verbatim):
BP7 BP4
Curation rationale (ClinGen, verbatim)
This synonymous variant (no REVEL score applicable) has SpliceAI scores ≤0.20 (0.01) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score < 2.0 (0.522) (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 1.4 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 9.912 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.00156% | 64,022 |
| European (non-Finnish)grpmax | 8.48e-05% | 1,179,930 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- RUNX1
- Protein
- p.Arg271=
- Coding
- c.813G>A
- MANE Select
- NM_001754
- dbSNP
- rs763723245
- Type
- single nucleotide variant
- Location
- chr21:34799455 (GRCh38)
- Gene constraint
- LOEUF 0.633 · pLI 0.29 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.76 · 5 PDB
Disease context
hereditary thrombocytopenia and hematologic cancer predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
For Familial platelet disorder with associated myeloid malignancy (Orphanet):
- Inheritance
- Autosomal dominant
Similar variants
- RUNX1 p.Arg271Lys Benign ★★★ same residue
- RUNX1 p.Arg271fs Likely pathogenic ★★★ same residue
- RUNX1 c.351+1G>A Pathogenic ★★★ same condition
- RUNX1 c.351+1G>C Likely pathogenic ★★★ same condition
- RUNX1 c.351+1G>T Pathogenic ★★★ same condition
- RUNX1 c.351+2T>A Likely pathogenic ★★★ same condition
- RUNX1 c.351+2T>C Likely pathogenic ★★★ same condition
- RUNX1 c.352-1G>A Pathogenic ★★★ same condition
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/runx1-p-arg271 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown