SHOX p.Pro243fs
c.728del · rs757845999 · VCV805452
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 (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 4.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00255% | 39,158 |
| Admixed American | 0.00199% | 50,252 |
| African / African-American | 0.00142% | 70,466 |
| South Asian | 0.00121% | 82,322 |
| European (non-Finnish) | 8.75e-05% | 1,142,322 |
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
- SHOX
- Protein
- p.Pro243fs
- Coding
- c.728del
- MANE Select
- NM_000451
- dbSNP
- rs757845999
- Type
- Deletion
- Location
- chrX:644480 (GRCh38)
- Structure
- AlphaFold pLDDT 63.90
- Residue 243
- a UniProt-annotated variant site (in iss; likely pathogenic)
Similar variants
- SHOX p.Ser269fs Pathogenic ★ same condition
- SHOX p.Pro243Leu Uncertain significance ★ same residue
- SHOX p.Glu61fs Pathogenic same condition
- SHOX c.-19G>A Pathogenic/Likely pathogenic ★★ same condition
- SHOX p.Arg168Trp Pathogenic/Likely pathogenic ★★ same condition
- SHOX p.Arg173Cys Pathogenic ★★ same condition
- SHOX p.Arg173His Pathogenic/Likely pathogenic ★★ same condition
- SHOX p.Arg195Ter 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/shox-p-pro243fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown