Is XDH p.Asp595= (c.1785C>T) pathogenic?

XDH p.Asp595= (c.1785C>T) is classified Likely benign in XDH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-14). Ultra-rare (popmax 0.0201%, eas); Associated with xanthinuria type II.

What condition is associated with XDH p.Asp595= (c.1785C>T)?

XDH p.Asp595= (c.1785C>T) is associated with xanthinuria type II, xanthinuria type I (ClinVar).

How common is XDH p.Asp595= (c.1785C>T) in the general population?

XDH p.Asp595= (c.1785C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

How is Hereditary xanthinuria inherited?

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

XDH p.Asp595=

c.1785C>T · rs140066757 · VCV775709

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

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 -11	GERP -3.7
Overall
CADD	1.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,878 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00396% 64/1,614,232 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
African / African-American	0.00533%	18,768
European (non-Finnish)	0.00398%	25,107
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Admixed American	0.00167%	60,034
South Asian	0.0011%	91,086

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.Asp595=
Coding: c.1785C>T
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs140066757
Type: single nucleotide variant
Location: chr2:31372299 (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

Also linked: xanthinuria type I

For Hereditary xanthinuria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

XDH p.Asp595Glu 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
XDH p.Lys57Ter 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-asp595 (accessed [today's date]).

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