Is CTNS p.Val136fs (c.405dup) pathogenic?

CTNS p.Val136fs (c.405dup) is classified Pathogenic in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Val136fs (c.405dup)?

CTNS p.Val136fs (c.405dup) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Val136fs (c.405dup) in the general population?

CTNS p.Val136fs (c.405dup) is absent from gnomAD (gnomAD).

CTNS p.Val136fs

c.405dup · rs2507745496 · VCV2947243

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 0.53, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTNS
Protein: p.Val136fs
Coding: c.405dup
MANE Select: NM_004937
dbSNP: rs2507745496
Type: Duplication
Location: chr17:3655293 (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 136: an α-helix; the pq-loop 1 domain

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

Similar variants

CTNS p.Val136Gly Uncertain significance ★★ ⚠ same residue
CTNS p.Ser310fs Pathogenic ★★ same condition
CTNS p.Thr277fs Pathogenic ★★ same condition
CTNS p.Thr98fs Pathogenic ★★ same condition
CTNS p.Tyr281fs Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Val233fs Pathogenic ★★ same condition
CTNS p.Val257fs Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Asn196fs Likely 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-p-val136fs (accessed [today's date]).

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