Is PHEX p.Arg567Pro (c.1700G>C) pathogenic?

PHEX p.Arg567Pro (c.1700G>C) is classified Pathogenic/Likely pathogenic in PHEX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-02-27). AlphaMissense: likely pathogenic (0.7989); Absent from gnomAD v4.1; Associated with PHEX-related disorder.

What condition is associated with PHEX p.Arg567Pro (c.1700G>C)?

PHEX p.Arg567Pro (c.1700G>C) is associated with PHEX-related disorder (ClinVar).

How common is PHEX p.Arg567Pro (c.1700G>C) in the general population?

PHEX p.Arg567Pro (c.1700G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHEX p.Arg567Pro (c.1700G>C)?

AlphaMissense predicts likely pathogenic (score 0.7989) — an in-silico prediction, not a clinical call.

PHEX p.Arg567Pro

c.1700G>C · rs760870713 · VCV372459

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PHEX-related disorder

Computational evidence

Protein change
AlphaMissense	0.7989	likely pathogenic ✓ concordant with ClinVar
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -8.49	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.61	donor loss · deltas
Pangolin	Δ0.29	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PHEX
Protein: p.Arg567Pro
Coding: c.1700G>C
MANE Select: NM_000444
dbSNP: rs760870713
Type: single nucleotide variant
Location: chrX:22212958 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 567: the peptidase m13 domain; a UniProt-annotated variant site (in xlhrd)

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

Disease context

PHEX-related disorder

Similar variants

PHEX p.Arg567Ter Pathogenic ★★ same residue
PHEX p.Arg567= Likely pathogenic ★ same residue
PHEX p.Arg567Gln Likely benign ★ ⚠ same residue
PHEX c.118+1G>A Pathogenic/Likely pathogenic ★★ same condition
PHEX c.1302+1G>A Pathogenic ★★ same condition
PHEX c.1482+2T>A Pathogenic/Likely pathogenic ★★ same condition
PHEX c.1587-1G>A Pathogenic ★★ same condition
PHEX c.1645+1G>A Pathogenic/Likely 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-arg567pro (accessed [today's date]).

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