RUNX2 p.Pro488fs
c.1463del · VCV3649937
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
RUNX2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 6.8 | GERP 1.8, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- RUNX2
- Protein
- p.Pro488fs
- Coding
- c.1463del
- MANE Select
- NM_001024630
- Type
- Deletion
- Location
- chr6:45547201 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.02 · 4 PDB
- Residue 488
- 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)
Disease context
RUNX2-related disorder
Similar variants
- RUNX2 p.Arg100fs Likely pathogenic ★ same condition
- RUNX2 p.Gly461fs Likely pathogenic ★ same condition
- RUNX2 p.Leu122fs Likely pathogenic ★ same condition
- RUNX2 p.Lys38fs Likely pathogenic ★ same condition
- RUNX2 p.Tyr454fs Likely pathogenic ★ same condition
- RUNX2 p.Arg225Trp Pathogenic ★★ same condition
- RUNX2 p.Arg391Ter Pathogenic ★★ same condition
- RUNX2 p.Asp463fs Pathogenic/Likely 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/runx2-p-pro488fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown