Is XDH p.Pro132= (c.396C>G) pathogenic?

XDH p.Pro132= (c.396C>G) is classified Likely benign in XDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-19). Very rare (popmax 6.84e-05%); Associated with xanthinuria type II.

What condition is associated with XDH p.Pro132= (c.396C>G)?

XDH p.Pro132= (c.396C>G) is associated with xanthinuria type II (ClinVar).

How common is XDH p.Pro132= (c.396C>G) in the general population?

XDH p.Pro132= (c.396C>G) is very rare (popmax 6.84e-05%) (gnomAD).

How is Hereditary xanthinuria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

XDH p.Pro132=

c.396C>G · VCV4749366

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

xanthinuria type II

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 -6.4	GERP -3.7
Overall
CADD	0.029	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,828 alleles · very rare

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: XDH
Protein: p.Pro132=
Coding: c.396C>G
MANE Select: NM_003104 · reported on NM_000379
Type: single nucleotide variant
Location: chr2:31398610 (GRCh38)
Structure: AlphaFold pLDDT 98.06 · 3 PDB
Residue 132: a UniProt-annotated variant site (in hmnr8); a β-strand

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

Disease context

xanthinuria type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary xanthinuria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

XDH c.1602+1G>A Likely pathogenic ★★ same condition
XDH c.565-1G>A Likely pathogenic ★★ same condition
XDH p.Arg1283Ter Pathogenic ★★ same condition
XDH p.Arg228Ter Pathogenic/Likely pathogenic ★★ same condition
XDH p.Arg825Ter Pathogenic/Likely pathogenic ★★ same condition
XDH p.Gln251Ter Pathogenic/Likely pathogenic ★★ same condition
XDH p.Lys722Ter Pathogenic ★★ same condition
XDH c.3951+5G>T Uncertain significance ★★ 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/xdh-p-pro132 (accessed [today's date]).

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