Is CPZ p.Arg596Gln (c.1787G>A) pathogenic?

CPZ p.Arg596Gln (c.1787G>A) is classified Benign in CPZ (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-24). AlphaMissense: likely benign (0.0735); Low-frequency (popmax 4.32%, afr); Associated with CPZ-related disorder.

What condition is associated with CPZ p.Arg596Gln (c.1787G>A)?

CPZ p.Arg596Gln (c.1787G>A) is associated with CPZ-related disorder (ClinVar).

How common is CPZ p.Arg596Gln (c.1787G>A) in the general population?

CPZ p.Arg596Gln (c.1787G>A) is low-frequency (popmax 4.32%, afr) (gnomAD).

What do computational predictors say about CPZ p.Arg596Gln (c.1787G>A)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

CPZ p.Arg596Gln

c.1787G>A · rs61734020 · VCV3038299

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.32%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CPZ-related disorder

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.6	GERP -2.4
Regional constraint	o/e 1.60	unconstrained · MANE · 27 kb · p 7.4e-73 · regional, not allelic
Overall
CADD	0.226	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.32% African / African-American · 3,244/75,042 alleles

Filtering AF 4.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.15%

Overall 1.59% 25,639/1,613,602 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.32%	23
Middle Eastern	3.93%	25
Ashkenazi Jewishnot grpmax-eligible	2.29%	44
Remaining individualsnot grpmax-eligible	1.71%	58
Finnishnot grpmax-eligible	1.68%	60
East Asian	1.65%	60
European (non-Finnish)	1.46%	69
Admixed American	1.09%	92
South Asian	0.855%	117

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.Arg596Gln
Coding: c.1787G>A
MANE Select: NM_001014447
dbSNP: rs61734020
Type: single nucleotide variant
Location: chr4:8619445 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.33
Residue 596: the 'disordered' region

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-arg596gln (accessed [today's date]).

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