SHOX p.Pro67Arg
c.200C>G · rs765679079 · VCV1685109
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000763%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.635 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 5.3 | GERP 3.2, phastCons 0.28 |
| Regional constraint | o/e 1.14 | unconstrained · MANE · 14 kb · p 0.0034 · regional, not allelic |
| Overall | ||
| CADD | 21.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000763%
European (non-Finnish) · 9/1,179,850 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000558%
9/1,613,720 alleles · very rare
exomes 9/1,461,426 · genomes 0/152,294 · joint denominator
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.Pro67Arg
- Coding
- c.200C>G
- MANE Select
- NM_000451
- dbSNP
- rs765679079
- Type
- single nucleotide variant
- Location
- chrX:631097 (GRCh38)
- Structure
- AlphaFold pLDDT 63.90
Similar variants
- SHOX p.Pro67Ser 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-pro67arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown