Is CTNS p.Trp138Ter (c.414G>A) pathogenic?

CTNS p.Trp138Ter (c.414G>A) is classified Pathogenic in CTNS (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-01-19). Very rare (popmax 0.00924%, nfe); Associated with CTNS-related disorder.

What condition is associated with CTNS p.Trp138Ter (c.414G>A)?

CTNS p.Trp138Ter (c.414G>A) is associated with CTNS-related disorder, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Trp138Ter (c.414G>A) in the general population?

CTNS p.Trp138Ter (c.414G>A) is very rare (popmax 0.00924%, nfe) (gnomAD).

CTNS p.Trp138Ter

c.414G>A · rs113994205 · VCV4443

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00924%, nfe)

Conditions

CTNS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.28	gain · loss 0.22 · independent
Constraint at this position
Conservation	phyloP 8.5	GERP 0.53, phastCons 1
Overall
CADD	49.0	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 0.00924% European (non-Finnish) · 109/1,180,042 alleles

Filtering AF 0.00782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00688% 111/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00924%	10,826
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00134%	74,904

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.Trp138Ter
Coding: c.414G>A
dbSNP: rs113994205
Type: single nucleotide variant
Location: chr17:3655305 (GRCh38)

Full CTNS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CTNS-related disorder

Also linked: ocular cystinosis juvenile nephropathic cystinosis cystinosis nephropathic cystinosis

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-trp138ter (accessed [today's date]).

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