PHEX p.Asp448=
c.1344C>T · rs144911719 · VCV288052
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.769%, afr)
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 2.8 | GERP 0.58, phastCons 1 |
| Overall | ||
| CADD | 10.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.769%
African / African-American · 437/56,826 alleles
Filtering AF
0.709%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.686%
Overall
0.0411%
496/1,207,312 alleles · rare
exomes 244/1,096,414 · genomes 252/110,898 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.769% | 130 |
| Remaining individualsnot grpmax-eligible | 0.0631% | 1,585 |
| Admixed American | 0.0505% | 1,982 |
| Middle Eastern | 0.023% | 4,352 |
| European (non-Finnish) | 0.00056% | 178,699 |
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.Asp448=
- Coding
- c.1344C>T
- MANE Select
- NM_000444
- dbSNP
- rs144911719
- Type
- single nucleotide variant
- Location
- chrX:22133564 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 448
- the peptidase m13 domain
Similar variants
- PHEX p.Asp448fs 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
- 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-asp448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown