Is CTNS p.Ser234fs (c.699_700del) pathogenic?

CTNS p.Ser234fs (c.699700del) is classified Pathogenic in CTNS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-28). Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Ser234fs (c.699_700del)?

CTNS p.Ser234fs (c.699_700del) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Ser234fs (c.699_700del) in the general population?

CTNS p.Ser234fs (c.699_700del) is very rare (popmax 0.00017%, nfe) (gnomAD).

CTNS p.Ser234fs

c.699_700del · rs766981777 · VCV1425663

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.7	GERP -3.4
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,938 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,610,332 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,284
European (non-Finnish)grpmax	0.00017%	589,971

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
Protein: p.Ser234fs
Coding: c.699_700del
MANE Select: NM_004937
dbSNP: rs766981777
Type: Microsatellite
Location: chr17:3658020 (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

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.Ser86fs 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-ser234fs (accessed [today's date]).

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