Is CTNS p.Ile69= (c.207C>T) pathogenic?

CTNS p.Ile69= (c.207C>T) is classified Likely benign in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-03). Very rare (popmax 0.00534%, afr); Associated with juvenile nephropathic cystinosis.

What condition is associated with CTNS p.Ile69= (c.207C>T)?

CTNS p.Ile69= (c.207C>T) is associated with juvenile nephropathic cystinosis, ocular cystinosis (ClinVar).

How common is CTNS p.Ile69= (c.207C>T) in the general population?

CTNS p.Ile69= (c.207C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

CTNS p.Ile69=

c.207C>T · rs765304748 · VCV1672615

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

juvenile nephropathic cystinosis

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 1	GERP 1.7, phastCons 1
Overall
CADD	10.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,872 alleles

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

Overall 0.00031% 5/1,612,688 alleles · very rare exomes 3/1,460,506 · genomes 2/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,718
Remaining individualsnot grpmax-eligible	0.0016%	62,440

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.Ile69=
Coding: c.207C>T
MANE Select: NM_004937
dbSNP: rs765304748
Type: single nucleotide variant
Location: chr17:3648913 (GRCh38)
Gene constraint: LOEUF 0.754 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB
Residue 69: a β-strand; a UniProt-annotated variant site (in ctnsjan; protein misfolding leading to decreased stability; decreased cystine transport)

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

Disease context

juvenile nephropathic cystinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ocular cystinosis

Similar variants

CTNS p.Ile69fs Pathogenic ★ same residue
CTNS c.140+1G>T Pathogenic/Likely pathogenic ★★ same condition
CTNS c.140+2T>C Pathogenic/Likely pathogenic ★★ same condition
CTNS c.141-1G>A Pathogenic/Likely pathogenic ★★ same condition
CTNS c.141-24T>C Pathogenic ★★ same condition
CTNS c.225+3A>T Pathogenic/Likely pathogenic ★★ same condition
CTNS c.225+5G>A Likely pathogenic ★★ same condition
CTNS c.61+2T>C Likely pathogenic ★★ same condition

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-ile69 (accessed [today's date]).

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