SHOX p.Phe241=
c.723C>T · rs886042718 · VCV283837
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0153%, eas)
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 0.66 | GERP 6, phastCons 1 |
| Overall | ||
| CADD | 11.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0153%
East Asian · 6/39,226 alleles
Filtering AF
0.00658%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00449%
Overall
0.000854%
13/1,522,570 alleles · ultra-rare
exomes 12/1,370,404 · genomes 1/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0153% | 6,538 |
| European (non-Finnish) | 0.000613% | 163,192 |
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.Phe241=
- Coding
- c.723C>T
- MANE Select
- NM_000451
- dbSNP
- rs886042718
- Type
- single nucleotide variant
- Location
- chrX:644480 (GRCh38)
- Structure
- AlphaFold pLDDT 63.90
- Residue 241
- a UniProt-annotated variant site (in iss; likely pathogenic)
Similar variants
- SHOX p.Phe241Leu 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-phe241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown