Is XDH p.Ile703Val (c.2107A>G) pathogenic?

XDH p.Ile703Val (c.2107A>G) is classified Benign/Likely benign in XDH (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0778); Common (popmax 11.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with xanthinuria type II.

What condition is associated with XDH p.Ile703Val (c.2107A>G)?

XDH p.Ile703Val (c.2107A>G) is associated with xanthinuria type II, xanthinuria type I (ClinVar).

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.Ile703Val (c.2107A>G)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

XDH p.Ile703Val

Q: How common is XDH p.Ile703Val (c.2107A>G) in the general population?

XDH p.Ile703Val (c.2107A>G) is common (popmax 11.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2107A>G · rs17011368 · VCV255966

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.7%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xanthinuria type II

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 1
Overall
CADD	21.1	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 11.7% African / African-American · 8,748/75,018 alleles

Filtering AF 11.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.4%

Overall 3.64% 58,759/1,613,932 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.7%	9
Middle Eastern	5.41%	18
Ashkenazi Jewishnot grpmax-eligible	5.26%	19
Remaining individualsnot grpmax-eligible	3.78%	26
European (non-Finnish)	3.38%	30
Finnishnot grpmax-eligible	3.06%	33
Admixed American	2.63%	38
South Asian	2.57%	39
Amishnot grpmax-eligible	0.44%	228
East Asian	0.107%	935

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.Ile703Val
Coding: c.2107A>G
MANE Select: NM_003104 · reported on NM_000379
dbSNP: rs17011368
Type: single nucleotide variant
Location: chr2:31368051 (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.Ile703Lys 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-ile703val (accessed [today's date]).

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