SHOX p.Ser41=
c.123C>T · VCV3895644
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00712%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.92 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 11.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00712%
European (non-Finnish) · 84/1,179,846 alleles
Filtering AF
0.00588%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00541%
Overall
0.00589%
95/1,613,666 alleles · very rare
exomes 87/1,461,550 · genomes 8/152,116 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00712% | 14,046 |
| Admixed American | 0.00667% | 14,999 |
| African / African-American | 0.00534% | 18,724 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
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.Ser41=
- Coding
- c.123C>T
- MANE Select
- NM_000451
- Type
- single nucleotide variant
- Location
- chrX:631020 (GRCh38)
- Structure
- AlphaFold pLDDT 63.90
Similar variants
- 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
- SHOX c.277+20G>C Uncertain significance ★★ 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-ser41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown