Is CHAMP1 p.Pro532= (c.1596C>T) pathogenic?

CHAMP1 p.Pro532= (c.1596C>T) is classified Likely benign in CHAMP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-06). Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with CHAMP1 p.Pro532= (c.1596C>T)?

CHAMP1 p.Pro532= (c.1596C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHAMP1 p.Pro532= (c.1596C>T) in the general population?

CHAMP1 p.Pro532= (c.1596C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CHAMP1 p.Pro532=

c.1596C>T · rs781893314 · VCV3025832

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

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 -1.3	GERP -3.4, phastCons 0.001
Overall
CADD	4.198	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 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00198% 32/1,613,942 alleles · ultra-rare exomes 31/1,461,888 · genomes 1/152,054 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Finnishnot grpmax-eligible	0.00625%	16,002
East Asian	0.00445%	22,448
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00169%	59,001

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.Pro532=
Coding: c.1596C>T
MANE Select: NM_032436
dbSNP: rs781893314
Type: single nucleotide variant
Location: chr13:114325438 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.04 · 4 PDB
Residue 532: 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.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
CHAMP1 p.Pro477Ser 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-pro532 (accessed [today's date]).

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