Is CTSO p.Arg288Trp (c.862C>T) pathogenic?

CTSO p.Arg288Trp (c.862C>T) is classified Uncertain significance in CTSO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: ambiguous (0.3423); Very rare (popmax 0.00835%, amr).

How common is CTSO p.Arg288Trp (c.862C>T) in the general population?

CTSO p.Arg288Trp (c.862C>T) is very rare (popmax 0.00835%, amr) (gnomAD).

What do computational predictors say about CTSO p.Arg288Trp (c.862C>T)?

AlphaMissense predicts ambiguous (score 0.3423) — an in-silico prediction, not a clinical call.

CTSO p.Arg288Trp

c.862C>T · rs773065737 · VCV2261111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3423 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

Computational evidence

Protein change
AlphaMissense	0.3423	ambiguous
REVEL	0.378	indeterminate
SaProt	LLR -13.19	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP -2.2, phastCons 0.89
Overall
CADD	26.6	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 0.00835% Admixed American · 5/59,864 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00416% 67/1,612,034 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,973
African / African-American	0.00803%	12,459
South Asian	0.0044%	22,718
European (non-Finnish)	0.00433%	23,116
East Asian	0.00223%	44,744

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.Arg288Trp
Coding: c.862C>T
MANE Select: NM_000396 · reported on NM_001334
dbSNP: rs773065737
Type: single nucleotide variant
Location: chr4:155928405 (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.Arg288Gln 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-arg288trp (accessed [today's date]).

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