RUNX2 p.Pro313=
c.939G>A · rs768076425 · VCV2980044
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 -1.1 | GERP -5.6 |
| Overall | ||
| CADD | 10.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,876 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000434%
7/1,613,886 alleles · very rare
exomes 4/1,461,850 · genomes 3/152,036 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,438 |
| Admixed American | 0.00167% | 59,986 |
| South Asian | 0.0011% | 91,084 |
| European (non-Finnish) | 0.000254% | 393,338 |
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.Pro313=
- Coding
- c.939G>A
- MANE Select
- NM_001024630
- dbSNP
- rs768076425
- Type
- single nucleotide variant
- Location
- chr6:45512325 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.02 · 4 PDB
- Residue 313
- a UniProt-annotated variant site (in clcd1; decreased subcellular localization in the nucleus; decreased transactivation activity); the 'disordered' region
Similar variants
- RUNX2 p.Pro313Gln Uncertain significance ★★ ⚠ same residue
- RUNX2 p.Pro313Arg Uncertain significance ★ ⚠ same residue
- RUNX2 p.Pro313fs 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
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-pro313 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown