PHEX p.Trp520Ter
c.1559G>A · rs2518606202 · VCV2117393
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Hypophosphataemia or rickets
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 14 of 22 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 43.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PHEX
- Protein
- p.Trp520Ter
- Coding
- c.1559G>A
- MANE Select
- NM_000444
- dbSNP
- rs2518606202
- Type
- single nucleotide variant
- Location
- chrX:22178349 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 520
- the peptidase m13 domain
Disease context
Hypophosphataemia or rickets
Similar variants
- PHEX c.118+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PHEX c.1302+1G>A Pathogenic ★★ same condition
- PHEX c.1482+2T>A Pathogenic/Likely pathogenic ★★ same condition
- PHEX c.1587-1G>A Pathogenic ★★ same condition
- PHEX c.1645+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PHEX c.732+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PHEX c.849+1G>A Pathogenic ★★ same condition
- PHEX c.849+1G>T Pathogenic ★★ same condition
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-trp520ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown