Is CPZ p.Cys122= (c.366C>T) pathogenic?

CPZ p.Cys122= (c.366C>T) is classified Likely benign in CPZ (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-11). Rare (popmax 0.117%, nfe); Associated with CPZ-related disorder.

What condition is associated with CPZ p.Cys122= (c.366C>T)?

CPZ p.Cys122= (c.366C>T) is associated with CPZ-related disorder (ClinVar).

How common is CPZ p.Cys122= (c.366C>T) in the general population?

CPZ p.Cys122= (c.366C>T) is rare (popmax 0.117%, nfe) (gnomAD).

CPZ p.Cys122=

c.366C>T · rs143245050 · VCV3045123

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.117%, nfe)

Conditions

CPZ-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 -7.2	GERP -2.1
Overall
CADD	0.785	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.117% European (non-Finnish) · 1,376/1,171,670 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.0905% 1,449/1,600,734 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.117%	852
Finnishnot grpmax-eligible	0.0492%	2,031
Remaining individualsnot grpmax-eligible	0.0485%	2,062
African / African-American	0.0107%	9,321
Admixed American	0.00506%	19,754
South Asian	0.00111%	89,860

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: CPZ
Protein: p.Cys122=
Coding: c.366C>T
MANE Select: NM_001014447
dbSNP: rs143245050
Type: single nucleotide variant
Location: chr4:8601367 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.33
Residue 122: a disulfide bond; the fz domain

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

Disease context

CPZ-related disorder

Similar variants

CPZ p.Ala205Thr Uncertain significance ⚠ same condition
CPZ p.Gly575Arg Uncertain significance ⚠ same condition
CPZ c.1363+6G>T Benign same condition
CPZ c.1504-3C>T Benign same condition
CPZ c.497-5C>G Likely benign same condition
CPZ c.-10C>T Likely benign same condition
CPZ c.*4C>T Benign same condition
CPZ c.*7C>G Likely benign 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/cpz-p-cys122 (accessed [today's date]).

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