Is CTSZ p.Arg189= (c.567G>A) pathogenic?

CTSZ p.Arg189= (c.567G>A) is classified Likely benign in CTSZ (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Rare (popmax 0.928%, nfe).

How common is CTSZ p.Arg189= (c.567G>A) in the general population?

CTSZ p.Arg189= (c.567G>A) is rare (popmax 0.928%, nfe) (gnomAD).

CTSZ p.Arg189=

c.567G>A · rs11540881 · VCV2652451

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.928%, nfe)

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 -3.1	GERP -4.7
Overall
CADD	1.182	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.928% European (non-Finnish) · 10,933/1,178,132 alleles

Filtering AF 0.913% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.907%

Overall 0.794% 12,785/1,609,850 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.27%	19
Ashkenazi Jewishnot grpmax-eligible	2.57%	39
European (non-Finnish)grpmax	0.928%	108
Remaining individualsnot grpmax-eligible	0.813%	123
Middle Eastern	0.479%	209
Admixed American	0.342%	292
African / African-American	0.169%	590
Finnishnot grpmax-eligible	0.119%	842
South Asian	0.108%	926
East Asian	0.00895%	11,176

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CTSZ
Protein: p.Arg189=
Coding: c.567G>A
MANE Select: NM_001336
dbSNP: rs11540881
Type: single nucleotide variant
Location: chr20:58997674 (GRCh38)
Gene constraint: LOEUF 1.628 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.35 · 2 PDB

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

Similar variants

CTSZ p.Gly191Arg Benign ★★ ⚠ same type
CTSZ p.Leu196Pro Benign/Likely benign ★★ same type
CTSZ p.Thr226Ser Benign ★★ ⚠ same type
CTSZ p.Ala144Thr Uncertain significance ★ ⚠ same type
CTSZ p.Ala18Ser Uncertain significance ★ ⚠ same type
CTSZ p.Ala18Val Uncertain significance ★ ⚠ same type
CTSZ p.Ala60Glu Uncertain significance ★ ⚠ same type
CTSZ p.Ala60Val Uncertain significance ★ ⚠ 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/ctsz-p-arg189 (accessed [today's date]).

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