Is CTNS p.Ser86fs (c.257_258del) pathogenic?

CTNS p.Ser86fs (c.257258del) is classified Pathogenic in CTNS (ClinVar, Single submitter, 3 submitters; last evaluated 2023-09-09). Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Ser86fs (c.257_258del)?

CTNS p.Ser86fs (c.257_258del) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Ser86fs (c.257_258del) in the general population?

CTNS p.Ser86fs (c.257_258del) is very rare (popmax 0.00223%, eas) (gnomAD).

CTNS p.Ser86fs

c.257_258del · rs879255614 · VCV253206

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP 1.9, phastCons 0.029

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 0.000137% 2/1,461,712 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	8.48e-05%	1,179,860

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.Ser86fs
Coding: c.257_258del
MANE Select: NM_004937
dbSNP: rs879255614
Type: Microsatellite
Location: chr17:3655027 (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 86: a β-strand

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 cystinosis nephropathic cystinosis

Similar variants

CTNS c.225+5_225+8del Likely pathogenic ★★ same condition
CTNS p.Asp205del Pathogenic ★★ same condition
CTNS p.Ser234fs Pathogenic ★★ same condition
CTNS p.Phe208del Uncertain significance ★ 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
CTNS c.971-8_971-6del 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-ser86fs (accessed [today's date]).

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