Is PHEX p.Gln133= (c.399G>A) pathogenic?

PHEX p.Gln133= (c.399G>A) is classified Benign/Likely benign in PHEX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-01). Absent from gnomAD v4.1.

How common is PHEX p.Gln133= (c.399G>A) in the general population?

PHEX p.Gln133= (c.399G>A) is absent from gnomAD v4.1 (gnomAD).

PHEX p.Gln133=

c.399G>A · rs1602273860 · VCV792809

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.6	GERP 1.6, phastCons 1
Overall
CADD	8.096	PHRED · no single calibrated threshold — expert panels disagree

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.Gln133=
Coding: c.399G>A
MANE Select: NM_000444
dbSNP: rs1602273860
Type: single nucleotide variant
Location: chrX:22076437 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 133: the peptidase m13 domain

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

Similar variants

PHEX p.Gln133Ter Pathogenic ★★ same residue
PHEX p.Gln133Glu Conflicting classifications of pathogenicity ★ ⚠ 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
PHEX c.1080-3C>G Pathogenic ★★ same type
PHEX c.1173+1G>A 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-gln133 (accessed [today's date]).

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