RUNX2 p.Pro471=
c.1413G>A · rs114897742 · VCV1110727
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, amr)
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 0.91 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 11.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
Admixed American · 12/60,010 alleles
Filtering AF
0.0115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00898%
Overall
0.0013%
21/1,614,048 alleles · ultra-rare
exomes 20/1,461,876 · genomes 1/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.02% | 5,001 |
| East Asian | 0.00446% | 22,439 |
| South Asian | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000508% | 196,669 |
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.Pro471=
- Coding
- c.1413G>A
- MANE Select
- NM_001024630
- dbSNP
- rs114897742
- Type
- single nucleotide variant
- Location
- chr6:45547152 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.02 · 4 PDB
- Residue 471
- a UniProt-annotated variant site (in clcd1; decreased subcellular localization in the nucleus; decreased transactivation activity); a UniProt-annotated variant site (in clcd1; unchanged subcellular localization; decreased transactivation activity); the 'disordered' region; a UniProt-annotated variant site (in clcd1; decreased protein stability; decreased transactivation activity; decreased osteoblast differentiation)
Similar variants
- RUNX2 p.Pro471Leu Uncertain significance ★ ⚠ 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
- RUNX2 p.Arg193Gln Pathogenic/Likely 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-pro471 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown