Is CTNS p.Asp205del (c.611ACG[1]) pathogenic?

CTNS p.Asp205del (c.611ACG[1]) is classified Pathogenic in CTNS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-29). Very rare (popmax 0.00447%, eas); Associated with cystinosis.

What condition is associated with CTNS p.Asp205del (c.611ACG[1])?

CTNS p.Asp205del (c.611ACG[1]) is associated with cystinosis, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Asp205del (c.611ACG[1]) in the general population?

CTNS p.Asp205del (c.611ACG[1]) is very rare (popmax 0.00447%, eas) (gnomAD).

How is Cystinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CTNS p.Asp205del

c.611ACG[1] · rs760256854 · VCV188718

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Conditions

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 1.4, phastCons 1
Overall
CADD	18.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,780 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000744% 12/1,613,238 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,390
Admixed American	0.00167%	59,948
European (non-Finnish)	0.000763%	131,101

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.Asp205del
Coding: c.611ACG[1]
MANE Select: NM_004937
dbSNP: rs760256854
Type: Microsatellite
Location: chr17:3656725 (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 205: an α-helix; a binding site; a UniProt-annotated variant site (in ctns; abolished cystine transport; abolished steady-state transport current; decreased midpoint potential); a UniProt-annotated variant site (in ctns; abolished cystine transport)

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

Disease context

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

Also linked: ocular cystinosis juvenile nephropathic cystinosis nephropathic cystinosis

For Cystinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

CTNS p.Asp205= Likely benign ★★ same residue
CTNS c.225+5_225+8del Likely pathogenic ★★ same condition
CTNS p.Ser234fs Pathogenic ★★ same condition
CTNS p.Ser86fs Pathogenic ★ same condition
CTNS p.Asp205Glu Uncertain significance ★ ⚠ same residue
CTNS p.Phe208del Uncertain significance ★ same condition
CTNS p.Phe350del Uncertain significance ★ same condition
CTNS c.853-10_853-7del Likely benign ★ 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-asp205del (accessed [today's date]).

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