Is XDH p.Pro579= (c.1737C>G) pathogenic?

XDH p.Pro579= (c.1737C>G) is classified Likely benign in XDH (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-21). Very rare (popmax 0.00267%, afr); Associated with xanthinuria type II.

What condition is associated with XDH p.Pro579= (c.1737C>G)?

XDH p.Pro579= (c.1737C>G) is associated with xanthinuria type II (ClinVar).

How common is XDH p.Pro579= (c.1737C>G) in the general population?

XDH p.Pro579= (c.1737C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Hereditary xanthinuria inherited?

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

XDH p.Pro579=

c.1737C>G · rs376148012 · VCV1558585

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 -0.61	GERP -3.7
Overall
CADD	2.416	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,954 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,477
European (non-Finnish)	0.000508%	196,674

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.Pro579=
Coding: c.1737C>G
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs376148012
Type: single nucleotide variant
Location: chr2:31372347 (GRCh38)
Structure: AlphaFold pLDDT 98.06 · 3 PDB

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 p.Pro579Ser Uncertain significance ★ ⚠ same residue
XDH p.Pro579Leu Uncertain significance ★ ⚠ same residue
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

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-pro579 (accessed [today's date]).

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