Is CTNS p.Ala256Leu (c.766_767delinsTT) pathogenic?

CTNS p.Ala256Leu (c.766767delinsTT) is classified Uncertain significance in CTNS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-04-23). Absent from gnomAD; Associated with juvenile nephropathic cystinosis.

What condition is associated with CTNS p.Ala256Leu (c.766_767delinsTT)?

CTNS p.Ala256Leu (c.766_767delinsTT) is associated with juvenile nephropathic cystinosis, ocular cystinosis, nephropathic cystinosis (ClinVar).

How common is CTNS p.Ala256Leu (c.766_767delinsTT) in the general population?

CTNS p.Ala256Leu (c.766_767delinsTT) is absent from gnomAD (gnomAD).

CTNS p.Ala256Leu

c.766_767delinsTT · rs1567713916 · VCV591047

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 1.6	GERP 0.59, phastCons 0.004
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.4 · regional, not allelic

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.Ala256Leu
Coding: c.766_767delinsTT
MANE Select: NM_004937
dbSNP: rs1567713916
Type: Indel
Location: chr17:3658089 (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 256: 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.Ala256= Likely benign ★ same residue
CTNS c.225+5_225+6delinsCC Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Ile272fs Likely pathogenic ★ same condition
CTNS c.140+1G>C Likely pathogenic ★★ same condition
CTNS c.140+1G>T Pathogenic/Likely pathogenic ★★ same condition
CTNS c.140+2T>C Pathogenic/Likely pathogenic ★★ same condition
CTNS c.141-1G>A Pathogenic/Likely pathogenic ★★ same condition
CTNS c.141-24T>C 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-ala256leu (accessed [today's date]).

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