Is XDH p.Arg787Pro (c.2360G>C) pathogenic?

XDH p.Arg787Pro (c.2360G>C) is classified Uncertain significance in XDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely pathogenic (0.9825); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with XDH p.Arg787Pro (c.2360G>C)?

XDH p.Arg787Pro (c.2360G>C) is associated with Inborn genetic diseases (ClinVar).

How common is XDH p.Arg787Pro (c.2360G>C) in the general population?

XDH p.Arg787Pro (c.2360G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about XDH p.Arg787Pro (c.2360G>C)?

AlphaMissense predicts likely pathogenic (score 0.9825) — an in-silico prediction, not a clinical call.

XDH p.Arg787Pro

c.2360G>C · VCV4634892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9825 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9825	likely pathogenic · top 5% in XDH
REVEL	0.361	indeterminate
SaProt	LLR -9.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: XDH
Protein: p.Arg787Pro
Coding: c.2360G>C
MANE Select: NM_003104 · reported on NM_000379
Type: single nucleotide variant
Location: chr2:31366072 (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

Similar variants

XDH p.Arg787Trp Uncertain significance ★★ same residue
XDH p.Arg787Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
SORD p.Ala153Asp Pathogenic/Likely pathogenic ★★ same condition
SORD p.Ile44Val Uncertain significance ★★ ⚠ same condition
SORD p.Val92Leu Uncertain significance ★★ ⚠ same condition
XDH p.Ala1120Thr Uncertain significance ★★ ⚠ same condition
XDH p.Ala544Thr Uncertain significance ★★ ⚠ same condition
XDH p.Ala582Val Uncertain significance ★★ ⚠ 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-arg787pro (accessed [today's date]).

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