Is XDH p.Val629Phe (c.1885G>T) pathogenic?

XDH p.Val629Phe (c.1885G>T) is classified Uncertain significance in XDH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1106); Ultra-rare (popmax 0.0646%, nfe); Associated with xanthinuria type II.

What condition is associated with XDH p.Val629Phe (c.1885G>T)?

XDH p.Val629Phe (c.1885G>T) is associated with xanthinuria type II, xanthinuria type I (ClinVar).

How common is XDH p.Val629Phe (c.1885G>T) in the general population?

XDH p.Val629Phe (c.1885G>T) is ultra-rare (popmax 0.0646%, nfe) (gnomAD).

How is Hereditary xanthinuria inherited?

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

What do computational predictors say about XDH p.Val629Phe (c.1885G>T)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

XDH p.Val629Phe

c.1885G>T · rs148464316 · VCV571131

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0646%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xanthinuria type II

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -10.85	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.8, phastCons 1
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0646% European (non-Finnish) · 762/1,180,020 alleles

Filtering AF 0.0607% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0592%

Overall 0.0541% 874/1,614,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0832%	1,202
European (non-Finnish)grpmax	0.0646%	1,549
African / African-American	0.044%	2,274
Middle Eastern	0.033%	3,031
Admixed American	0.015%	6,669
East Asian	0.0111%	8,976
South Asian	0.00878%	11,385
Finnishnot grpmax-eligible	0.00468%	21,346

Remaining individuals 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.Val629Phe
Coding: c.1885G>T
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs148464316
Type: single nucleotide variant
Location: chr2:31370450 (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.Val629Ile Benign/Likely benign ★★ same residue
XDH p.Val629Leu Uncertain significance ★ ⚠ same residue
XDH p.Val629fs Likely 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

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-val629phe (accessed [today's date]).

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