SHOX p.Pro219=
c.657G>A · rs28474801 · VCV586580
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 88.9%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.62 | phastCons 0.002 |
| Overall | ||
| CADD | 0.455 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
88.9%
African / African-American · 40,370/45,418 alleles
Filtering AF
88.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 87.9%
Overall
64.7%
248,928/384,448 alleles · common
exomes 145,133/237,004 · genomes 103,795/147,444 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 88.9% | 1 |
| East Asian | 70.6% | 1 |
| Middle Eastern | 68.4% | 1 |
| South Asian | 67.6% | 1 |
| Amishnot grpmax-eligible | 64.1% | 2 |
| Remaining individualsnot grpmax-eligible | 62.9% | 2 |
| European (non-Finnish) | 60.8% | 2 |
| Admixed American | 58.4% | 2 |
| Finnishnot grpmax-eligible | 55.4% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 55% | 2 |
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.Pro219=
- Coding
- c.657G>A
- MANE Select
- NM_000451 · reported on NM_006883
- dbSNP
- rs28474801
- Type
- single nucleotide variant
- Location
- chrX:658808 (GRCh38)
- Structure
- AlphaFold pLDDT 63.90
- Residue 219
- a UniProt-annotated variant site (in iss; likely pathogenic)
Similar variants
- SHOX p.Pro219Ser 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-pro219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown