PHEX p.Cys746=
c.2238C>T · VCV4702229
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00034%, nfe)
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 1.1 | GERP 0.68, phastCons 1 |
| Overall | ||
| CADD | 7.798 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00034%
European (non-Finnish) · 3/882,102 alleles
Filtering AF
9.1e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.5e-05%
Overall
0.000251%
3/1,197,263 alleles · very rare
exomes 3/1,083,444 · genomes 0/113,819 · 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
- PHEX
- Protein
- p.Cys746=
- Coding
- c.2238C>T
- MANE Select
- NM_000444
- Type
- single nucleotide variant
- Location
- chrX:22247941 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 746
- a disulfide bond; the peptidase m13 domain; a UniProt-annotated variant site (in xlhrd)
Similar variants
- PHEX p.Cys746Arg Likely pathogenic ★★ same residue
- PHEX p.Cys746Phe Likely pathogenic ★★ same residue
- PHEX p.Cys746Ter Pathogenic ★ same residue
- PHEX c.1079+1G>A Pathogenic ★★ same type
- PHEX c.1079+2T>G Pathogenic ★★ same type
- PHEX c.1080-1G>A Pathogenic ★★ same type
- PHEX c.1080-2A>G Pathogenic ★★ same type
- PHEX c.1080-3C>G 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/phex-p-cys746 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown