Is CTNS p.Phe208del (c.619TTC[1]) pathogenic?

CTNS p.Phe208del (c.619TTC[1]) is classified Uncertain significance in CTNS (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-17). Very rare (popmax 0.00167%, amr); Associated with juvenile nephropathic cystinosis.

What condition is associated with CTNS p.Phe208del (c.619TTC[1])?

CTNS p.Phe208del (c.619TTC[1]) is associated with juvenile nephropathic cystinosis, ocular cystinosis, nephropathic cystinosis (ClinVar).

How common is CTNS p.Phe208del (c.619TTC[1]) in the general population?

CTNS p.Phe208del (c.619TTC[1]) is very rare (popmax 0.00167%, amr) (gnomAD).

CTNS p.Phe208del

c.619TTC[1] · rs1555563619 · VCV557383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 9.7	GERP 0.43, phastCons 1
Overall
CADD	18.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,962 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,613,322 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,962
South Asian	0.0011%	91,054
European (non-Finnish)	0.000424%	235,994

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.Phe208del
Coding: c.619TTC[1]
MANE Select: NM_004937
dbSNP: rs1555563619
Type: Microsatellite
Location: chr17:3656731 (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 208: an α-helix

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 p.Phe208= Likely benign ★ same residue
CTNS c.225+5_225+8del Likely pathogenic ★★ same condition
CTNS p.Asp205del Pathogenic ★★ same condition
CTNS p.Ser234fs Pathogenic ★★ same condition
CTNS p.Ser86fs Pathogenic ★ same condition
CTNS p.Phe350del Uncertain significance ★ same condition
CTNS c.853-10_853-7del Likely benign ★ same condition
CTNS c.853-18_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-phe208del (accessed [today's date]).

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