Is CPZ p.Pro568= (c.1704C>T) pathogenic?

CPZ p.Pro568= (c.1704C>T) is classified Benign in CPZ (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-16). Low-frequency (popmax 1.42%, sas); Associated with CPZ-related disorder.

What condition is associated with CPZ p.Pro568= (c.1704C>T)?

CPZ p.Pro568= (c.1704C>T) is associated with CPZ-related disorder (ClinVar).

How common is CPZ p.Pro568= (c.1704C>T) in the general population?

CPZ p.Pro568= (c.1704C>T) is low-frequency (popmax 1.42%, sas) (gnomAD).

CPZ p.Pro568=

c.1704C>T · rs34486568 · VCV3042600

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.42%, sas)

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 -12	GERP -3
Overall
CADD	0.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.42% South Asian · 1,296/91,076 alleles

Filtering AF 1.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.33%

Overall 0.492% 7,947/1,614,192 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.42%	70
Amishnot grpmax-eligible	0.768%	130
European (non-Finnish)	0.501%	199
Remaining individualsnot grpmax-eligible	0.394%	254
Middle Eastern	0.379%	264
Finnishnot grpmax-eligible	0.353%	283
Ashkenazi Jewishnot grpmax-eligible	0.226%	442
African / African-American	0.125%	799
Admixed American	0.112%	896
East Asian	0.0134%	7,480

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.Pro568=
Coding: c.1704C>T
MANE Select: NM_001014447
dbSNP: rs34486568
Type: single nucleotide variant
Location: chr4:8619362 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.33

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-pro568 (accessed [today's date]).

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