Is CTNS p.Ile178= (c.534C>T) pathogenic?

CTNS p.Ile178= (c.534C>T) is classified Benign in CTNS (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-14). Rare (popmax 0.189%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Ile178= (c.534C>T)?

CTNS p.Ile178= (c.534C>T) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Ile178= (c.534C>T) in the general population?

CTNS p.Ile178= (c.534C>T) is rare (popmax 0.189%, afr) (gnomAD).

CTNS p.Ile178=

c.534C>T · rs113967200 · VCV715414

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.189%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.7	GERP -3.1
Overall
CADD	2.948	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.189% African / African-American · 139/73,678 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.0105% 169/1,610,588 alleles · rare exomes 89/1,461,650 · genomes 80/148,938 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.189%	530
Admixed American	0.0168%	5,951
Remaining individualsnot grpmax-eligible	0.00961%	10,407
South Asian	0.0022%	45,420
European (non-Finnish)	0.00102%	98,277

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.Ile178=
Coding: c.534C>T
MANE Select: NM_004937
dbSNP: rs113967200
Type: single nucleotide variant
Location: chr17:3656559 (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 178: an α-helix; the pq-loop 1 domain

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 cystinosis

Similar variants

CTNS p.Ile178Val Uncertain significance ★ ⚠ same residue
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

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-ile178 (accessed [today's date]).

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