PHEX p.Lys280=
c.840G>A · rs147430384 · VCV2417227
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.118%, afr)
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 5.7 | GERP 0.14, phastCons 1 |
| Overall | ||
| CADD | 11.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.118%
African / African-American · 65/55,218 alleles
Filtering AF
0.0948%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0863%
Overall
0.00887%
97/1,093,772 alleles · rare
exomes 68/981,417 · genomes 29/112,355 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.118% | 850 |
| Middle Eastern | 0.0493% | 2,029 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,246 |
| Admixed American | 0.0132% | 7,589 |
| South Asian | 0.0129% | 7,733 |
| European (non-Finnish) | 0.00127% | 79,021 |
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.Lys280=
- Coding
- c.840G>A
- MANE Select
- NM_000444
- dbSNP
- rs147430384
- Type
- single nucleotide variant
- Location
- chrX:22094090 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 280
- the peptidase m13 domain
Similar variants
- 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
- PHEX c.1173+5G>C 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/phex-p-lys280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown