Is CTSO p.Arg288Gln (c.863G>A) pathogenic?

CTSO p.Arg288Gln (c.863G>A) is classified Uncertain significance in CTSO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.0987); Ultra-rare (popmax 0.0281%, afr).

How common is CTSO p.Arg288Gln (c.863G>A) in the general population?

CTSO p.Arg288Gln (c.863G>A) is ultra-rare (popmax 0.0281%, afr) (gnomAD).

What do computational predictors say about CTSO p.Arg288Gln (c.863G>A)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CTSO p.Arg288Gln

c.863G>A · rs138871272 · VCV2595814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -8.50	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 4	GERP 0.62, phastCons 0.92
Overall
CADD	23.6	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 0.0281% African / African-American · 21/74,820 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00298% 48/1,612,444 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0281%	3,563
Remaining individualsnot grpmax-eligible	0.00641%	15,601
Admixed American	0.00501%	19,963
South Asian	0.0033%	30,299
Finnishnot grpmax-eligible	0.00156%	63,998
European (non-Finnish)	0.00136%	73,697

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: CTSO
Protein: p.Arg288Gln
Coding: c.863G>A
MANE Select: NM_000396 · reported on NM_001334
dbSNP: rs138871272
Type: single nucleotide variant
Location: chr4:155928404 (GRCh38)
Structure: AlphaFold pLDDT 94.89 · 70 PDB
Residue 288: a disulfide bond

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

Similar variants

CTSO p.Arg288Trp Uncertain significance ★ ⚠ same residue
CTSK p.Gly288= Likely benign ★ same residue
CTSK c.121-1G>A Pathogenic/Likely pathogenic ★★ same type
CTSK c.121-2A>G Pathogenic/Likely pathogenic ★★ same type
CTSK c.244-29A>G Pathogenic/Likely pathogenic ★★ same type
CTSK c.244-2A>C Likely pathogenic ★★ same type
CTSK c.400-1G>C Likely pathogenic ★★ same type
CTSK c.784+1G>A 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/ctso-p-arg288gln (accessed [today's date]).

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