PHEX p.Lys251=
c.753G>A · rs2519772018 · VCV1991392
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000567%, nfe)
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 1.9 | GERP -0.34, phastCons 1 |
| Overall | ||
| CADD | 7.336 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000567%
European (non-Finnish) · 5/882,491 alleles
Filtering AF
0.000166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000121%
Overall
0.000418%
5/1,196,574 alleles · very rare
exomes 5/1,082,833 · genomes 0/113,741 · 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.Lys251=
- Coding
- c.753G>A
- MANE Select
- NM_000444
- dbSNP
- rs2519772018
- Type
- single nucleotide variant
- Location
- chrX:22094003 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 251
- the peptidase m13 domain
Similar variants
- PHEX p.Lys251Glu Uncertain significance ★★ ⚠ same residue
- PHEX p.Lys251fs 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
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-lys251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown