Is CTNS p.Ile220= (c.660C>T) pathogenic?

CTNS p.Ile220= (c.660C>T) is classified Likely benign in CTNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-22). Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Ile220= (c.660C>T)?

CTNS p.Ile220= (c.660C>T) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Ile220= (c.660C>T) in the general population?

CTNS p.Ile220= (c.660C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

CTNS p.Ile220=

c.660C>T · rs369227591 · VCV1116147

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.82	GERP -2.8
Overall
CADD	5.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,914 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000496% 8/1,613,262 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,728
South Asian	0.0011%	91,088
European (non-Finnish)	0.000254%	393,335

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: CTNS
Protein: p.Ile220=
Coding: c.660C>T
dbSNP: rs369227591
Type: single nucleotide variant
Location: chr17:3656774 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ocular cystinosis juvenile nephropathic cystinosis

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/ctns-p-ile220 (accessed [today's date]).

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