Is CHAMP1 p.Pro508Arg (c.1523C>G) pathogenic?

CHAMP1 p.Pro508Arg (c.1523C>G) is classified Uncertain significance in CHAMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely benign (0.1407); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHAMP1 p.Pro508Arg (c.1523C>G)?

CHAMP1 p.Pro508Arg (c.1523C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHAMP1 p.Pro508Arg (c.1523C>G) in the general population?

CHAMP1 p.Pro508Arg (c.1523C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHAMP1 p.Pro508Arg (c.1523C>G)?

AlphaMissense predicts likely benign (score 0.1407) — an in-silico prediction, not a clinical call.

CHAMP1 p.Pro508Arg

c.1523C>G · VCV3491879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1407 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1407	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -4.80	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 2.6	GERP 1.7, phastCons 0.16
Regional constraint	o/e 1.21	unconstrained · MANE · 1,781 bp · p 1.6e-08 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: CHAMP1
Protein: p.Pro508Arg
Coding: c.1523C>G
MANE Select: NM_032436
Type: single nucleotide variant
Location: chr13:114325365 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.04 · 4 PDB
Residue 508: the 'disordered' region; the 'mediates localization to the spindle and the kinetochore and is required for the attachment of spindle microtubules to the kinetochore' region

Full CHAMP1 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

CHAMP1 p.Pro508Thr Uncertain significance ★ ⚠ same residue
CHAMP1 p.Ala304Val Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Glu195Gly Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Glu668Gln Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Gly238Arg Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Met671Thr Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Pro150Leu Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Pro265Ser 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/champ1-p-pro508arg (accessed [today's date]).

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