Is CTNS p.Gln319Ter (c.955C>T) pathogenic?

CTNS p.Gln319Ter (c.955C>T) is classified Pathogenic/Likely pathogenic in CTNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Very rare (popmax 8.48e-05%, nfe); Associated with cystinosis.

What condition is associated with CTNS p.Gln319Ter (c.955C>T)?

CTNS p.Gln319Ter (c.955C>T) is associated with cystinosis, nephropathic cystinosis (ClinVar).

How common is CTNS p.Gln319Ter (c.955C>T) in the general population?

CTNS p.Gln319Ter (c.955C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Cystinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CTNS p.Gln319Ter

c.955C>T · rs2142981652 · VCV2681026

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

cystinosis

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (11 of 12, 15 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Overall
CADD	47.0	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 8.48e-05% European (non-Finnish) · 1/1,179,802 alleles

Overall 6.84e-05% 1/1,461,160 alleles · very rare

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.Gln319Ter
Coding: c.955C>T
MANE Select: NM_004937
dbSNP: rs2142981652
Type: single nucleotide variant
Location: chr17:3659960 (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 319: an α-helix; the pq-loop 2 domain

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

Disease context

cystinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephropathic cystinosis

For Cystinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

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.141-24T>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-gln319ter (accessed [today's date]).

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