Is XDH p.Cys48= (c.144C>T) pathogenic?

XDH p.Cys48= (c.144C>T) is classified Likely benign in XDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). Ultra-rare (popmax 0.055%, amr); Associated with xanthinuria type II.

What condition is associated with XDH p.Cys48= (c.144C>T)?

XDH p.Cys48= (c.144C>T) is associated with xanthinuria type II (ClinVar).

How common is XDH p.Cys48= (c.144C>T) in the general population?

XDH p.Cys48= (c.144C>T) is ultra-rare (popmax 0.055%, amr) (gnomAD).

How is Hereditary xanthinuria inherited?

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

XDH p.Cys48=

c.144C>T · rs369196176 · VCV2198710

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.055%, amr)

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 -2.5	GERP -4
Overall
CADD	3.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.055% Admixed American · 33/60,010 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.0044% 71/1,614,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.055%	1,818
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921
Middle Eastern	0.0164%	6,084
South Asian	0.00878%	11,386
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00161%	62,107

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.Cys48=
Coding: c.144C>T
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs369196176
Type: single nucleotide variant
Location: chr2:31403101 (GRCh38)
Structure: AlphaFold pLDDT 98.06 · 3 PDB
Residue 48: an α-helix

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.Cys48fs Pathogenic ★★ 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.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-cys48 (accessed [today's date]).

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