Is CIZ1 p.Pro409= (c.1227C>A) pathogenic?

CIZ1 p.Pro409= (c.1227C>A) is classified Benign in CIZ1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 10.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with dystonic disorder.

What condition is associated with CIZ1 p.Pro409= (c.1227C>A)?

CIZ1 p.Pro409= (c.1227C>A) is associated with dystonic disorder (ClinVar).

CIZ1 p.Pro409=

Q: How common is CIZ1 p.Pro409= (c.1227C>A) in the general population?

CIZ1 p.Pro409= (c.1227C>A) is common (popmax 10.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1227C>A · rs45559035 · VCV413831

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

dystonic 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 -0.06	GERP -5.3, phastCons 0.003
Overall
CADD	0.549	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.4% East Asian · 4,665/44,842 alleles

Filtering AF 10.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.1%

Overall 0.714% 11,519/1,613,508 alleles · common exomes 10,324/1,461,786 · genomes 1,195/151,722 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	10.4%	10
Finnishnot grpmax-eligible	3.66%	27
South Asian	3.12%	32
Remaining individualsnot grpmax-eligible	1.06%	94
Middle Eastern	0.281%	356
Ashkenazi Jewishnot grpmax-eligible	0.196%	510
African / African-American	0.0815%	1,227
European (non-Finnish)	0.0718%	1,393
Admixed American	0.04%	2,499

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: CIZ1
Protein: p.Pro409=
Coding: c.1227C>A
MANE Select: NM_001131016
dbSNP: rs45559035
Type: single nucleotide variant
Location: chr9:128178980 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.51 · 1 PDB
Residue 409: the 'disordered' region

Full CIZ1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIZ1 p.Ala128Ser Uncertain significance ★★ ⚠ same condition
CIZ1 p.Ala345Val Uncertain significance ★★ ⚠ same condition
CIZ1 p.Ala523Ser Uncertain significance ★★ ⚠ same condition
CIZ1 p.Ala833Gly Uncertain significance ★★ ⚠ same condition
CIZ1 p.Arg286Gln Uncertain significance ★★ ⚠ same condition
CIZ1 p.Arg571His Uncertain significance ★★ ⚠ same condition
CIZ1 p.Arg640Gln Uncertain significance ★★ ⚠ same condition
CIZ1 p.Arg865His 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/ciz1-p-pro409 (accessed [today's date]).

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