Is CTNS p.Cys224Ter (c.672C>A) pathogenic?

CTNS p.Cys224Ter (c.672C>A) is classified Likely pathogenic in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-02). Absent from gnomAD v4.1; Associated with cystinosis.

What condition is associated with CTNS p.Cys224Ter (c.672C>A)?

CTNS p.Cys224Ter (c.672C>A) is associated with cystinosis (ClinVar).

How common is CTNS p.Cys224Ter (c.672C>A) in the general population?

CTNS p.Cys224Ter (c.672C>A) is absent from gnomAD v4.1 (gnomAD).

How is Cystinosis inherited?

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

CTNS p.Cys224Ter

c.672C>A · rs2507764701 · VCV1726091

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP 1.4, phastCons 0.71
Overall
CADD	36.0	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

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.Cys224Ter
Coding: c.672C>A
MANE Select: NM_004937
dbSNP: rs2507764701
Type: single nucleotide variant
Location: chr17:3656786 (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 224: an α-helix

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

For Cystinosis (Orphanet):

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

Similar variants

CTNS p.Cys224Arg Uncertain significance ★ ⚠ same residue
CTNS c.140+2T>C Pathogenic/Likely 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+5G>A Pathogenic/Likely pathogenic ★★ same condition
CTNS c.681+1G>A Pathogenic ★★ same condition
CTNS c.682-1G>T Pathogenic/Likely pathogenic ★★ same condition
CTNS c.853-2A>G 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-cys224ter (accessed [today's date]).

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