PHEX p.Ser542=
c.1626T>C · rs752810184 · VCV2177324
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0404%, 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 -0.14 | GERP -4.2, phastCons 0.74 |
| Overall | ||
| CADD | 7.077 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0404%
African / African-American · 23/56,948 alleles
Filtering AF
0.0276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0234%
Overall
0.00201%
24/1,192,774 alleles · ultra-rare
exomes 12/1,080,345 · genomes 12/112,429 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0404% | 2,476 |
| Admixed American | 0.00218% | 45,788 |
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.Ser542=
- Coding
- c.1626T>C
- MANE Select
- NM_000444
- dbSNP
- rs752810184
- Type
- single nucleotide variant
- Location
- chrX:22190483 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 542
- the peptidase m13 domain
Similar variants
- PHEX p.Ser542Asn Uncertain significance ★ ⚠ same residue
- PHEX p.Ser542Thr Uncertain significance ★ ⚠ 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-ser542 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown