RUNX2 p.Arg100=
c.300C>T · rs1304152411 · VCV2049231
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 7.2 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 16.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,816 alleles
Filtering AF
0.000555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000208%
Overall
0.000124%
2/1,608,990 alleles · very rare
exomes 1/1,457,048 · genomes 1/151,942 · joint denominator
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
- RUNX2
- Protein
- p.Arg100=
- Coding
- c.300C>T
- MANE Select
- NM_001024630
- dbSNP
- rs1304152411
- Type
- single nucleotide variant
- Location
- chr6:45422834 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.02 · 4 PDB
- Residue 100
- a UniProt-annotated variant site (in clcd1; decreased subcellular localization in the nucleus; decreased transactivation activity)
Similar variants
- RUNX2 p.Arg100Ser Uncertain significance ★★ ⚠ same residue
- RUNX2 p.Arg100fs Likely pathogenic ★ same residue
- RUNX2 c.860-1G>A Likely pathogenic ★★ same type
- RUNX2 c.860-1G>T Pathogenic/Likely pathogenic ★★ same type
- RUNX2 p.Ala362Val Pathogenic ★★ ⚠ same type
- RUNX2 p.Arg169Trp Pathogenic/Likely pathogenic ★★ same type
- RUNX2 p.Arg190Gln Pathogenic ★★ same type
- RUNX2 p.Arg190Trp Pathogenic ★★ 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/runx2-p-arg100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown