Is PHEX p.Glu217fs (c.649_650del) pathogenic?

PHEX p.Glu217fs (c.649650del) is classified Likely pathogenic in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-07). Associated with PHEX-related disorder.

What condition is associated with PHEX p.Glu217fs (c.649_650del)?

PHEX p.Glu217fs (c.649_650del) is associated with PHEX-related disorder (ClinVar).

PHEX p.Glu217fs

c.649_650del · VCV4949308

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

PHEX-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP 0.28

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PHEX
Protein: p.Glu217fs
Coding: c.649_650del
MANE Select: NM_000444
Type: Deletion
Location: chrX:22077688 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 217: the peptidase m13 domain

Full PHEX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PHEX-related disorder

Similar variants

PHEX p.Glu217Ter Pathogenic ★★ same residue
PHEX p.Gly6fs Pathogenic ★★ same condition
PHEX p.Phe409fs Pathogenic ★★ same condition
PHEX p.Arg166fs Likely pathogenic ★ same condition
PHEX p.Gln621fs Likely pathogenic ★ same condition
PHEX p.Lys359fs Likely pathogenic ★ same condition
PHEX p.Phe389fs Pathogenic ★ same condition
PHEX p.Asn110del Conflicting classifications of pathogenicity ★ same condition

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-glu217fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown