Is CPZ p.Ser311Arg (c.933C>G) pathogenic?

CPZ p.Ser311Arg (c.933C>G) is classified Uncertain significance in CPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely pathogenic (0.7058); Ultra-rare (popmax 0.0134%, eas).

How common is CPZ p.Ser311Arg (c.933C>G) in the general population?

CPZ p.Ser311Arg (c.933C>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CPZ p.Ser311Arg (c.933C>G)?

AlphaMissense predicts likely pathogenic (score 0.7058) — an in-silico prediction, not a clinical call.

CPZ p.Ser311Arg

c.933C>G · VCV3269326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7058 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7058	likely pathogenic
REVEL	0.08	moderately benign-leaning
SaProt	LLR -3.39	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -2.5
Regional constraint	o/e 1.60	unconstrained · MANE · 27 kb · p 7.4e-73 · regional, not allelic
Overall
CADD	4.747	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 0.0134% East Asian · 6/44,880 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000479% 7/1,461,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
European (non-Finnish)	8.47e-05%	1,180,025

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.Ser311Arg
Coding: c.933C>G
MANE Select: NM_001014447
Type: single nucleotide variant
Location: chr4:8606763 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.33
Residue 311: the peptidase m14 domain

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

Similar variants

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
CPZ p.Gln263Arg Benign ★★ ⚠ same type
CPZ p.Pro618= 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-ser311arg (accessed [today's date]).

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