RUNX2 p.Pro320=
c.960G>A · rs139514226 · VCV1611254
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
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 0.44 | GERP -5.6, phastCons 0.98 |
| Overall | ||
| CADD | 12.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,084 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00062%
10/1,613,826 alleles · very rare
exomes 9/1,461,838 · genomes 1/151,988 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,771 |
| African / African-American | 0.00267% | 37,415 |
| East Asian | 0.00223% | 44,886 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 0.000169% | 590,002 |
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.Pro320=
- Coding
- c.960G>A
- MANE Select
- NM_001024630
- dbSNP
- rs139514226
- Type
- single nucleotide variant
- Location
- chr6:45512346 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.02 · 4 PDB
- Residue 320
- a UniProt-annotated variant site (in clcd1; decreased subcellular localization in the nucleus; decreased transactivation activity); the 'disordered' region
Similar variants
- RUNX2 p.Pro320Leu Uncertain significance ★★ ⚠ same residue
- RUNX2 p.Pro320fs 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-pro320 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown