Is PHEX p.Ala573Pro (c.1717G>C) pathogenic?

PHEX p.Ala573Pro (c.1717G>C) is classified Pathogenic in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-04). AlphaMissense: likely pathogenic (0.9958); Absent from gnomAD v4.1.

How common is PHEX p.Ala573Pro (c.1717G>C) in the general population?

PHEX p.Ala573Pro (c.1717G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHEX p.Ala573Pro (c.1717G>C)?

AlphaMissense predicts likely pathogenic (score 0.9958) — an in-silico prediction, not a clinical call.

PHEX p.Ala573Pro

c.1717G>C · rs1057520756 · VCV379848

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9958 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9958	likely pathogenic ✓ concordant with ClinVar · top 4% in PHEX
REVEL	0.891	moderately pathogenic-leaning
SaProt	LLR -13.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	29.6	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.Ala573Pro
Coding: c.1717G>C
MANE Select: NM_000444
dbSNP: rs1057520756
Type: single nucleotide variant
Location: chrX:22219052 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 573: 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

Similar variants

PHEX p.Ala573Asp Pathogenic/Likely pathogenic ★★ same residue
PHEX p.Ala573Val Likely pathogenic ★★ same residue
PHEX p.Ala573Thr Uncertain significance ★ ⚠ same residue
PHEX p.Ala573fs Pathogenic ★ same residue
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

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-ala573pro (accessed [today's date]).

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