Is CHAMP1 p.Pro422= (c.1266C>T) pathogenic?

CHAMP1 p.Pro422= (c.1266C>T) is classified Likely benign in CHAMP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-18). Ultra-rare (popmax 0.0164%, mid); Associated with CHAMP1-related disorder.

What condition is associated with CHAMP1 p.Pro422= (c.1266C>T)?

CHAMP1 p.Pro422= (c.1266C>T) is associated with CHAMP1-related disorder (ClinVar).

How common is CHAMP1 p.Pro422= (c.1266C>T) in the general population?

CHAMP1 p.Pro422= (c.1266C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CHAMP1 p.Pro422=

c.1266C>T · rs782283006 · VCV3040024

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

CHAMP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -3.4, phastCons 0.5
Overall
CADD	2.852	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00149% 24/1,614,016 alleles · ultra-rare exomes 21/1,461,890 · genomes 3/152,126 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.0147%	6,808
South Asian	0.0022%	45,542
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000763%	131,116

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: CHAMP1
Protein: p.Pro422=
Coding: c.1266C>T
MANE Select: NM_032436
dbSNP: rs782283006
Type: single nucleotide variant
Location: chr13:114325108 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.04 · 4 PDB
Residue 422: the 'disordered' region; the 'mediates interaction with mad2l2' region

Full CHAMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHAMP1-related disorder

Similar variants

CHAMP1 p.Arg398Ter Pathogenic ★★ same condition
CHAMP1 p.Arg497Ter Pathogenic ★★ same condition
CHAMP1 p.Glu687Lys Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Asp593Asn Uncertain significance ★ ⚠ same condition
CHAMP1 p.Ile351Val Uncertain significance ★ ⚠ same condition
CHAMP1 p.Pro159Leu Uncertain significance ★ ⚠ same condition
CHAMP1 p.Gln657Ter Pathogenic same condition
CHAMP1 p.Glu553Ter 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/champ1-p-pro422 (accessed [today's date]).

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