Is CHAMP1 p.Pro488Ser (c.1462C>T) pathogenic?

CHAMP1 p.Pro488Ser (c.1462C>T) is classified Uncertain significance in CHAMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-22). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1.

How common is CHAMP1 p.Pro488Ser (c.1462C>T) in the general population?

CHAMP1 p.Pro488Ser (c.1462C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHAMP1 p.Pro488Ser (c.1462C>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

CHAMP1 p.Pro488Ser

c.1462C>T · rs2087232190 · VCV2136014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.62	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 1.1	GERP -0.32, phastCons 0.99
Regional constraint	o/e 1.21	unconstrained · MANE · 1,781 bp · p 1.6e-08 · regional, not allelic
Overall
CADD	12.05	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.Pro488Ser
Coding: c.1462C>T
MANE Select: NM_032436
dbSNP: rs2087232190
Type: single nucleotide variant
Location: chr13:114325304 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.04 · 4 PDB
Residue 488: the 'disordered' region; the 'mediates interaction with mad2l2' 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

Similar variants

CHAMP1 p.Arg398Ter Pathogenic ★★ same type
CHAMP1 p.Arg497Ter Pathogenic ★★ same type
CHAMP1 p.Lys620Ter Pathogenic ★★ same type
CHAMP1 p.Tyr709Ter Pathogenic/Likely pathogenic ★★ same type
CHAMP1 p.Ala304Val Uncertain significance ★★ ⚠ same type
CHAMP1 p.Glu195Gly Uncertain significance ★★ ⚠ same type
CHAMP1 p.Glu524Gly Uncertain significance ★★ ⚠ same type
CHAMP1 p.Glu668Gln Uncertain significance ★★ ⚠ same type

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-pro488ser (accessed [today's date]).

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