Is PHEX p.Gln402= (c.1206A>G) pathogenic?

PHEX p.Gln402= (c.1206A>G) is classified Benign in PHEX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Low-frequency (popmax 3.29%, afr); Associated with X-linked dominant hypophosphatemic rickets.

What condition is associated with PHEX p.Gln402= (c.1206A>G)?

PHEX p.Gln402= (c.1206A>G) is associated with X-linked dominant hypophosphatemic rickets (ClinVar).

How common is PHEX p.Gln402= (c.1206A>G) in the general population?

PHEX p.Gln402= (c.1206A>G) is low-frequency (popmax 3.29%, afr) (gnomAD).

How is X-linked hypophosphatemia inherited?

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

PHEX p.Gln402=

c.1206A>G · rs151234075 · VCV368167

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.29%, afr)

Conditions

X-linked dominant hypophosphatemic rickets

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.4
Overall
CADD	0.996	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.29% African / African-American · 1,871/56,922 alleles

Filtering AF 3.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.11%

Overall 0.185% 2,214/1,195,884 alleles · low-frequency exomes 1,173/1,084,123 · genomes 1,041/111,761 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.29%	30
Admixed American	0.322%	310
Remaining individualsnot grpmax-eligible	0.252%	396
Middle Eastern	0.139%	720
South Asian	0.0124%	8,071
European (non-Finnish)	0.00725%	13,789

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PHEX
Protein: p.Gln402=
Coding: c.1206A>G
MANE Select: NM_000444
dbSNP: rs151234075
Type: single nucleotide variant
Location: chrX:22114490 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 402: 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 p.Gln402Ter Pathogenic ★★ same residue
PHEX c.1079+1G>A Pathogenic ★★ same condition
PHEX c.1079+2T>G Pathogenic ★★ same condition
PHEX c.1080-1G>A Pathogenic ★★ same condition
PHEX c.1080-3C>G Pathogenic ★★ same condition
PHEX c.1173+1G>A Pathogenic ★★ same condition
PHEX c.1173+5G>C Likely pathogenic ★★ same condition
PHEX c.1174-1G>A 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-gln402 (accessed [today's date]).

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