Is CPZ p.Ala301= (c.903C>G) pathogenic?

CPZ p.Ala301= (c.903C>G) is classified Benign in CPZ (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-12). Low-frequency (popmax 4.63%, sas); Associated with CPZ-related disorder.

What condition is associated with CPZ p.Ala301= (c.903C>G)?

CPZ p.Ala301= (c.903C>G) is associated with CPZ-related disorder (ClinVar).

How common is CPZ p.Ala301= (c.903C>G) in the general population?

CPZ p.Ala301= (c.903C>G) is low-frequency (popmax 4.63%, sas) (gnomAD).

CPZ p.Ala301=

c.903C>G · rs201543610 · VCV3033724

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 4.63%, 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 -8.1	GERP -4.2
Overall
CADD	0.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.63% South Asian · 4,213/90,960 alleles

Filtering AF 4.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.47%

Overall 0.275% 4,440/1,612,870 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4.63%	22
Middle Eastern	0.33%	303
Remaining individualsnot grpmax-eligible	0.259%	386
African / African-American	0.00933%	10,717
East Asian	0.00892%	11,213
Admixed American	0.005%	19,987
European (non-Finnish)	0.00263%	38,047

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.Ala301=
Coding: c.903C>G
MANE Select: NM_001014447
dbSNP: rs201543610
Type: single nucleotide variant
Location: chr4:8606182 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.33
Residue 301: the peptidase m14 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-ala301 (accessed [today's date]).

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