Is PHEX p.Phe724Ter (c.2167_2170dup) pathogenic?

PHEX p.Phe724Ter (c.21672170dup) is classified Pathogenic in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2015-08-18). No gnomAD frequency available for this variant; Associated with hypophosphatemic rickets.

What condition is associated with PHEX p.Phe724Ter (c.2167_2170dup)?

PHEX p.Phe724Ter (c.2167_2170dup) is associated with hypophosphatemic rickets (ClinVar).

How common is PHEX p.Phe724Ter (c.2167_2170dup) in the general population?

PHEX p.Phe724Ter (c.2167_2170dup) is no gnomAD frequency available for this variant (gnomAD).

PHEX p.Phe724Ter

c.2167_2170dup · rs1057518896 · VCV374096

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypophosphatemic rickets

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (22 of 22) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.4, 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.Phe724Ter
Coding: c.2167_2170dup
MANE Select: NM_000444
dbSNP: rs1057518896
Type: Duplication
Location: chrX:22247868 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 724: the peptidase m13 domain

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

Disease context

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

Similar variants

PHEX p.His329fs Pathogenic ★★ same condition
PHEX p.Phe724_Glu725insValPhePhePhePhePhePheXaaXaaXaaXaaValPheCysValAlaHisAlaGlySerCysArgProGluLeuPheLeuPheGlyHisLeuGlySerSerLeuProIleSerAsnPhe Pathogenic ★ same residue
PHEX p.Phe724fs Pathogenic ★ same residue
PHEX c.1482+2T>A Pathogenic/Likely pathogenic ★★ same condition
PHEX c.1700+2T>C Pathogenic ★★ same condition
PHEX c.1768+1G>C Pathogenic ★★ same condition
PHEX c.2071-1G>C Pathogenic ★★ same condition
PHEX c.663+1G>T Pathogenic ★★ 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-phe724ter (accessed [today's date]).

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