SHOX p.Arg280=
c.840G>C · rs914058289 · VCV994489
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0716%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP -0.23, phastCons 1 |
| Overall | ||
| CADD | 11.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0716%
African / African-American · 50/69,806 alleles
Filtering AF
0.0558%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0501%
Overall
0.00357%
54/1,511,466 alleles · ultra-rare
exomes 24/1,359,202 · genomes 30/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0716% | 1,396 |
| Remaining individualsnot grpmax-eligible | 0.00511% | 19,588 |
| Admixed American | 0.00204% | 49,012 |
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.Arg280=
- Coding
- c.840G>C
- MANE Select
- NM_000451
- dbSNP
- rs914058289
- Type
- single nucleotide variant
- Location
- chrX:644597 (GRCh38)
- Structure
- AlphaFold pLDDT 63.90
- Residue 280
- a UniProt-annotated variant site (in iss; likely pathogenic)
Similar variants
- SHOX p.Arg280Pro Uncertain significance ★★ same residue
- SHOX c.-19G>A Pathogenic/Likely pathogenic ★★ same type
- SHOX p.Arg168Trp Pathogenic/Likely pathogenic ★★ same type
- SHOX p.Arg173Cys Pathogenic ★★ same type
- SHOX p.Arg173His Pathogenic/Likely pathogenic ★★ same type
- SHOX p.Arg195Ter Pathogenic ★★ same type
- SHOX p.Cys194Ter Pathogenic ★★ same type
- SHOX p.Gln117Ter 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/shox-p-arg280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown