PHEX p.Gly441=
c.1323C>T · rs769336836 · VCV2159886
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0461%, mid)
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 0.21 | GERP -2.4, phastCons 0.99 |
| Overall | ||
| CADD | 2.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0461%
Middle Eastern · 2/4,342 alleles
Filtering AF
0.00814%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00341%
Overall
0.000497%
6/1,206,336 alleles · ultra-rare
exomes 6/1,093,471 · genomes 0/112,865 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0461% | 2,171 |
| East Asian | 0.00888% | 11,261 |
| South Asian | 0.00176% | 56,823 |
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.Gly441=
- Coding
- c.1323C>T
- MANE Select
- NM_000444
- dbSNP
- rs769336836
- Type
- single nucleotide variant
- Location
- chrX:22133543 (GRCh38)
- Structure
- AlphaFold pLDDT 94.58
- Residue 441
- 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-gly441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown