MSX2 p.Arg159fs
c.473dup · VCV4294501
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
2
parietal foramina with cleidocranial dysplasia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (2 of 2) — 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 2.1, phastCons 1 |
| Region caveats | ||
| Repeat context | seg dup | · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MSX2
- Protein
- p.Arg159fs
- Coding
- c.473dup
- MANE Select
- NM_002449
- Type
- Duplication
- Location
- chr5:174729251 (GRCh38)
- Gene constraint
- LOEUF 1.013 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.77
- Residue 159
- a DNA-binding region; a UniProt-annotated variant site (in pfm1; loss of function)
Similar variants
- MSX2 p.Arg159_Lys160del Pathogenic same residue
- MSX2 p.Arg159His Uncertain significance ★★ ⚠ same residue
- MSX2 p.Arg159Cys Uncertain significance ★ ⚠ same residue
- MSX2 p.Ala170fs Pathogenic same condition
- MSX2 p.Ala212Gly Uncertain significance ★★ ⚠ same condition
- MSX2 p.Pro251Ser Uncertain significance ★★ ⚠ same condition
- MSX2 c.380-164G>A Benign ★★ same condition
- MSX2 c.-17C>G Benign/Likely benign ★★ 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/msx2-p-arg159fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown