Is CPZ p.Arg68Trp (c.202C>T) pathogenic?

CPZ p.Arg68Trp (c.202C>T) is classified Uncertain significance in CPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.1208); Ultra-rare (popmax 0.0243%, nfe).

How common is CPZ p.Arg68Trp (c.202C>T) in the general population?

CPZ p.Arg68Trp (c.202C>T) is ultra-rare (popmax 0.0243%, nfe) (gnomAD).

What do computational predictors say about CPZ p.Arg68Trp (c.202C>T)?

AlphaMissense predicts likely benign (score 0.1208) — an in-silico prediction, not a clinical call.

CPZ p.Arg68Trp

c.202C>T · rs145749554 · VCV2405723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1208 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1208	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -9.09	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 -0.18	GERP -1.4, phastCons 0.001
Regional constraint	o/e 1.60	unconstrained · MANE · 27 kb · p 7.4e-73 · regional, not allelic
Overall
CADD	18.13	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0243% European (non-Finnish) · 287/1,179,686 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0211%

Overall 0.0199% 321/1,613,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0243%	4,110
Remaining individualsnot grpmax-eligible	0.0224%	4,463
Admixed American	0.01%	10,000
South Asian	0.00989%	10,116
African / African-American	0.00533%	18,763
East Asian	0.00223%	44,852

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.Arg68Trp
Coding: c.202C>T
MANE Select: NM_001014447
dbSNP: rs145749554
Type: single nucleotide variant
Location: chr4:8601203 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.33
Residue 68: a disulfide bond; the fz domain

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

Similar variants

CPZ p.Arg68Gln Uncertain significance ★ ⚠ same residue
CPZ p.Arg68Leu Uncertain significance ★ ⚠ same residue
CPZ p.Gln317Ter Uncertain significance ★★ same type
CPZ c.1068+9C>T Benign ★★ same type
CPZ c.1604-8G>T Benign ★★ same type
CPZ p.Arg522= Benign ★★ same type
CPZ p.Arg647= Likely benign ★★ same type
CPZ p.Asn250= Benign ★★ same type

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-arg68trp (accessed [today's date]).

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