Is CTNS p.Arg232Cys (c.694C>T) pathogenic?

CTNS p.Arg232Cys (c.694C>T) is classified Uncertain significance in CTNS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-30). AlphaMissense: likely benign (0.1053); Ultra-rare (popmax 0.0222%, mid); Associated with ocular cystinosis.

What condition is associated with CTNS p.Arg232Cys (c.694C>T)?

CTNS p.Arg232Cys (c.694C>T) is associated with ocular cystinosis, juvenile nephropathic cystinosis, nephropathic cystinosis (ClinVar).

How common is CTNS p.Arg232Cys (c.694C>T) in the general population?

CTNS p.Arg232Cys (c.694C>T) is ultra-rare (popmax 0.0222%, mid) (gnomAD).

How is Cystinosis inherited?

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

What do computational predictors say about CTNS p.Arg232Cys (c.694C>T)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

CTNS p.Arg232Cys

c.694C>T · rs138823792 · VCV322841

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0222%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ocular cystinosis

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.616	indeterminate
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.4 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0222% Middle Eastern · 1/4,496 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0116% 187/1,610,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0222%	4,496
African / African-American	0.0187%	5,348
European (non-Finnish)	0.0135%	7,421
Remaining individualsnot grpmax-eligible	0.00963%	10,379
South Asian	0.00659%	15,168
Admixed American	0.00167%	60,008

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.Arg232Cys
Coding: c.694C>T
MANE Select: NM_004937
dbSNP: rs138823792
Type: single nucleotide variant
Location: chr17:3658017 (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

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

Also linked: juvenile nephropathic cystinosis nephropathic cystinosis

For Cystinosis (Orphanet):

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

Similar variants

CTNS p.Arg232His Conflicting classifications of pathogenicity ★ ⚠ same residue
CTNS p.Arg232= Likely benign ★ same residue
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
CTNS c.225+3A>T 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-arg232cys (accessed [today's date]).

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