RUNX2 p.Ser409fs
c.1225dup · VCV4856176
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
cleidocranial dysplasia 1
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 12 | GERP 2.8, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- RUNX2
- Protein
- p.Ser409fs
- Coding
- c.1225dup
- MANE Select
- NM_001024630
- Type
- Duplication
- Location
- chr6:45546963 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.02 · 4 PDB
- Residue 409
- a UniProt-annotated variant site (in clcd1; decreased subcellular localization in the nucleus; decreased transactivation activity); the 'interaction with kat6a' region; the 'interaction with kat6b' region; a UniProt-annotated variant site (in clcd1; unchanged subcellular localization; decreased transactivation activity)
Similar variants
- RUNX2 p.Ser31fs Pathogenic ★★ same condition
- RUNX2 p.Gln438fs Pathogenic ★ same condition
- RUNX2 p.Leu410fs Pathogenic same condition
- RUNX2 p.Pro403fs Pathogenic same condition
- RUNX2 p.Thr11fs Pathogenic same condition
- RUNX2 p.Tyr213fs Pathogenic same condition
- RUNX2 c.860-1G>A Likely pathogenic ★★ same condition
- RUNX2 p.Arg169Trp 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-ser409fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown