PHEX p.Pro735=
c.2205C>T · VCV3616324
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00246%, 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 -0.2 | GERP -3.7 |
| Overall | ||
| CADD | 6.391 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00246%
European (non-Finnish) · 22/893,292 alleles
Filtering AF
0.00161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00138%
Overall
0.0019%
23/1,207,921 alleles · very rare
exomes 22/1,095,918 · genomes 1/112,003 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00246% | 40,604 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,532 |
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.Pro735=
- Coding
- c.2205C>T
- MANE Select
- NM_000444
- Type
- single nucleotide variant
- Location
- chrX:22247908 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 735
- the peptidase m13 domain
Similar variants
- PHEX p.Pro735Ser Likely benign ★ 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
- PHEX c.1173+1G>A Pathogenic ★★ same type
- PHEX c.1173+2T>C 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-pro735 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown