Is XDH p.Thr679= (c.2037A>C) pathogenic?

XDH p.Thr679= (c.2037A>C) is classified Conflicting classifications of pathogenicity in XDH (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-15). Rare (popmax 0.453%, afr); Associated with xanthinuria type I.

What condition is associated with XDH p.Thr679= (c.2037A>C)?

XDH p.Thr679= (c.2037A>C) is associated with xanthinuria type I, xanthinuria type II (ClinVar).

How common is XDH p.Thr679= (c.2037A>C) in the general population?

XDH p.Thr679= (c.2037A>C) is rare (popmax 0.453%, afr) (gnomAD).

How is Hereditary xanthinuria inherited?

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

XDH p.Thr679=

c.2037A>C · rs139998082 · VCV716067

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.453%, afr)

Conditions

xanthinuria type I

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 -0.52	GERP -3.7, phastCons 0.083
Overall
CADD	4.303	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.453% African / African-American · 340/75,048 alleles

Filtering AF 0.413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.398%

Overall 0.0222% 358/1,614,214 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.453%	221
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.01%	10,004
European (non-Finnish)	8.47e-05%	1,180,034

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.Thr679=
Coding: c.2037A>C
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs139998082
Type: single nucleotide variant
Location: chr2:31368604 (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 I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xanthinuria type II

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.Lys57Ter Likely pathogenic ★★ same condition
XDH p.Lys722Ter 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-thr679 (accessed [today's date]).

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