Is XDH p.Phe1006= (c.3018T>C) pathogenic?

XDH p.Phe1006= (c.3018T>C) is classified Conflicting classifications of pathogenicity in XDH (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0758%, nfe); Associated with xanthinuria type I.

What condition is associated with XDH p.Phe1006= (c.3018T>C)?

XDH p.Phe1006= (c.3018T>C) is associated with xanthinuria type I, xanthinuria type II (ClinVar).

How common is XDH p.Phe1006= (c.3018T>C) in the general population?

XDH p.Phe1006= (c.3018T>C) is ultra-rare (popmax 0.0758%, nfe) (gnomAD).

How is Hereditary xanthinuria inherited?

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

XDH p.Phe1006=

c.3018T>C · rs144883930 · VCV711191

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0758%, nfe)

Conditions

xanthinuria type I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.3	GERP 0.54, phastCons 1
Overall
CADD	9.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0758% European (non-Finnish) · 894/1,179,430 alleles

Filtering AF 0.0716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.07%

Overall 0.0632% 1,019/1,613,592 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.122%	821
European (non-Finnish)grpmax	0.0758%	1,319
Remaining individualsnot grpmax-eligible	0.048%	2,083
African / African-American	0.016%	6,254
Admixed American	0.00833%	12,006

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe1006=
Coding: c.3018T>C
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs144883930
Type: single nucleotide variant
Location: chr2:31348932 (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-phe1006 (accessed [today's date]).

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