Is CAT p.Arg189Cys (c.565C>T) pathogenic?

CAT p.Arg189Cys (c.565C>T) is classified Benign/Likely benign in CAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.2057); Rare (popmax 0.856%, eas).

How common is CAT p.Arg189Cys (c.565C>T) in the general population?

CAT p.Arg189Cys (c.565C>T) is rare (popmax 0.856%, eas) (gnomAD).

What do computational predictors say about CAT p.Arg189Cys (c.565C>T)?

AlphaMissense predicts likely benign (score 0.2057) — an in-silico prediction, not a clinical call.

CAT p.Arg189Cys

c.565C>T · rs78209054 · VCV716541

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2057 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.856%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2057	likely benign
REVEL	0.427	indeterminate
SaProt	LLR -7.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 32 kb · p 0.47 · regional, not allelic
Overall
CADD	28.6	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 0.856% East Asian · 384/44,840 alleles

Filtering AF 0.786% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.758%

Overall 0.0284% 457/1,609,164 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.856%	117
Remaining individualsnot grpmax-eligible	0.0561%	1,782
South Asian	0.0132%	7,579
African / African-American	0.00267%	37,463
European (non-Finnish)	0.00204%	48,980

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: CAT
Protein: p.Arg189Cys
Coding: c.565C>T
MANE Select: NM_001752
dbSNP: rs78209054
Type: single nucleotide variant
Location: chr11:34453174 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.97 · 17 PDB

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

Similar variants

CAT c.239-5G>A Benign/Likely benign ★★ same type
CAT p.Asn439= Likely benign ★★ same type
CAT p.Gly390Asp Benign ★★ same type
CAT p.His209Tyr Likely benign ★★ same type
CAT p.His492= Benign/Likely benign ★★ same type
CAT p.Ile109= Benign/Likely benign ★★ same type
CAT p.Phe185= Benign/Likely benign ★★ same type
CAT c.1057-2A>G Likely pathogenic ★ 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/cat-p-arg189cys (accessed [today's date]).

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