Is XDH p.Glu692Lys (c.2074G>A) pathogenic?

XDH p.Glu692Lys (c.2074G>A) is classified Uncertain significance in XDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely benign (0.1388); Very rare (popmax 8.47e-05%, nfe); Associated with xanthinuria type II.

What condition is associated with XDH p.Glu692Lys (c.2074G>A)?

XDH p.Glu692Lys (c.2074G>A) is associated with xanthinuria type II (ClinVar).

How common is XDH p.Glu692Lys (c.2074G>A) in the general population?

XDH p.Glu692Lys (c.2074G>A) is very rare (popmax 8.47e-05%, 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.Glu692Lys (c.2074G>A)?

AlphaMissense predicts likely benign (score 0.1388) — an in-silico prediction, not a clinical call.

XDH p.Glu692Lys

c.2074G>A · rs772739492 · VCV933541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

xanthinuria type II

Computational evidence

Protein change
AlphaMissense	0.1388	likely benign
REVEL	0.296	indeterminate
SaProt	LLR -10.28	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	25.0	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 0.000657% 1/152,164 alleles · very rare

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.Glu692Lys
Coding: c.2074G>A
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs772739492
Type: single nucleotide variant
Location: chr2:31368567 (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

For Hereditary xanthinuria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

XDH p.Glu692Asp Conflicting classifications of pathogenicity ★ ⚠ 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-glu692lys (accessed [today's date]).

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