Is CTNS p.Glu18Asp (c.54G>C) pathogenic?

CTNS p.Glu18Asp (c.54G>C) is classified Uncertain significance in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-10). AlphaMissense: likely benign (0.1204); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Glu18Asp (c.54G>C)?

CTNS p.Glu18Asp (c.54G>C) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Glu18Asp (c.54G>C) in the general population?

CTNS p.Glu18Asp (c.54G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNS p.Glu18Asp (c.54G>C)?

AlphaMissense predicts likely benign (score 0.1204) — an in-silico prediction, not a clinical call.

CTNS p.Glu18Asp

c.54G>C · VCV3761392

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1204 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1204	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.4 · regional, not allelic
Overall
CADD	17.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTNS
Protein: p.Glu18Asp
Coding: c.54G>C
MANE Select: NM_004937
Type: single nucleotide variant
Location: chr17:3640260 (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

Similar variants

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
CTNS c.225+3A>T Pathogenic/Likely pathogenic ★★ same condition
CTNS c.225+5G>A Likely pathogenic ★★ same condition
CTNS c.61+2T>C Likely pathogenic ★★ same condition
CTNS c.61+5G>A Pathogenic/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-glu18asp (accessed [today's date]).

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