Is PHEX p.Pro698fs (c.2092_2096del) pathogenic?

PHEX p.Pro698fs (c.20922096del) is classified Pathogenic in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). No gnomAD frequency available for this variant; Associated with X-linked dominant hypophosphatemic rickets.

What condition is associated with PHEX p.Pro698fs (c.2092_2096del)?

PHEX p.Pro698fs (c.2092_2096del) is associated with X-linked dominant hypophosphatemic rickets (ClinVar).

How common is PHEX p.Pro698fs (c.2092_2096del) in the general population?

PHEX p.Pro698fs (c.2092_2096del) is no gnomAD frequency available for this variant (gnomAD).

How is X-linked hypophosphatemia inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PHEX p.Pro698fs

c.2092_2096del · rs2147213985 · VCV1686053

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked dominant hypophosphatemic rickets

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 21 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHEX
Protein: p.Pro698fs
Coding: c.2092_2096del
MANE Select: NM_000444
dbSNP: rs2147213985
Type: Deletion
Location: chrX:22245350 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 698: the peptidase m13 domain

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

Disease context

X-linked dominant hypophosphatemic rickets — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked hypophosphatemia (Orphanet):

Inheritance: X-linked dominant
Onset: Childhood, Infancy
Prevalence: 1-9 / 100 000 (Norway)

Similar variants

PHEX c.1079+2_1079+5del Pathogenic ★★ same condition
PHEX c.187+1del Pathogenic ★★ same condition
PHEX p.Ala242fs Pathogenic ★★ same condition
PHEX p.Ala730fs Pathogenic ★★ same condition
PHEX p.Leu438fs Pathogenic ★★ same condition
PHEX p.Phe731fs Pathogenic/Likely pathogenic ★★ same condition
PHEX p.Trp520fs Pathogenic ★★ same condition
PHEX p.Pro698Ser Uncertain significance ★★ ⚠ same residue

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-pro698fs (accessed [today's date]).

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