Is XDH p.Pro1104Ser (c.3310C>T) pathogenic?

XDH p.Pro1104Ser (c.3310C>T) is classified Uncertain significance in XDH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-30). AlphaMissense: likely benign (0.2299); Very rare (popmax 0.0072%, nfe); Associated with Inborn genetic diseases.

What condition is associated with XDH p.Pro1104Ser (c.3310C>T)?

XDH p.Pro1104Ser (c.3310C>T) is associated with Inborn genetic diseases, xanthinuria type II (ClinVar).

How common is XDH p.Pro1104Ser (c.3310C>T) in the general population?

XDH p.Pro1104Ser (c.3310C>T) is very rare (popmax 0.0072%, nfe) (gnomAD).

What do computational predictors say about XDH p.Pro1104Ser (c.3310C>T)?

AlphaMissense predicts likely benign (score 0.2299) — an in-silico prediction, not a clinical call.

XDH p.Pro1104Ser

c.3310C>T · rs558670995 · VCV2060719

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2299	likely benign
REVEL	0.38	indeterminate
SaProt	LLR -10.85	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	26.1	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 0.0072% European (non-Finnish) · 85/1,180,022 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.0057% 92/1,613,906 alleles · very rare exomes 83/1,461,892 · genomes 9/152,014 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0072%	13,883
Admixed American	0.00667%	14,997
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00134%	74,848
South Asian	0.0011%	91,074

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.Pro1104Ser
Coding: c.3310C>T
MANE Select: NM_000379
dbSNP: rs558670995
Type: single nucleotide variant
Location: chr2:31346810 (GRCh38)
Structure: AlphaFold pLDDT 98.06 · 3 PDB

Full XDH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xanthinuria type II

Similar variants

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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-pro1104ser (accessed [today's date]).

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