Is CTNS c.226del pathogenic?

CTNS c.226del is classified Pathogenic/Likely pathogenic in CTNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-11). Very rare (popmax 0.00034%, nfe); Associated with juvenile nephropathic cystinosis.

What condition is associated with CTNS c.226del?

CTNS c.226del is associated with juvenile nephropathic cystinosis, ocular cystinosis, nephropathic cystinosis (ClinVar).

How common is CTNS c.226del in the general population?

CTNS c.226del is very rare (popmax 0.00034%, nfe) (gnomAD).

CTNS c.226del

rs867630648 · VCV2950669

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

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 · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Non-coding constraint	Z 2.40	1 kb window · o/e 0.79 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,176,230 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000311% 5/1,610,084 alleles · very rare exomes 5/1,457,798 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,394
European (non-Finnish)grpmax	0.00034%	294,057

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.226del
MANE Select: NM_004937
dbSNP: rs867630648
Type: Deletion
Location: chr17:3654997 (GRCh38)
Gene constraint: LOEUF 0.754 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB

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 nephropathic cystinosis

Similar variants

CTNS c.559_561+24del Pathogenic/Likely pathogenic ★★ same condition
CTNS c.561+1del Pathogenic/Likely pathogenic ★★ same condition
CTNS c.61_61+2del Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Gln108fs Pathogenic ★★ same condition
CTNS p.Gly258fs Pathogenic ★★ same condition
CTNS p.His105fs Pathogenic ★★ same condition
CTNS p.Phe9fs Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Pro13_Leu14insTer 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-c-226del (accessed [today's date]).

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