Is CTNS p.Asn36= (c.108C>T) pathogenic?

CTNS p.Asn36= (c.108C>T) is classified Benign/Likely benign in CTNS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Rare (popmax 0.923%, nfe); Associated with ocular cystinosis.

What condition is associated with CTNS p.Asn36= (c.108C>T)?

CTNS p.Asn36= (c.108C>T) is associated with ocular cystinosis, juvenile nephropathic cystinosis, cystinosis (ClinVar).

How common is CTNS p.Asn36= (c.108C>T) in the general population?

CTNS p.Asn36= (c.108C>T) is rare (popmax 0.923%, nfe) (gnomAD).

How is Cystinosis inherited?

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

CTNS p.Asn36=

c.108C>T · rs117404824 · VCV322835

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.923%, nfe)

Conditions

ocular cystinosis

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 -3	GERP -3.1
Overall
CADD	1.314	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.923% European (non-Finnish) · 10,895/1,180,010 alleles

Filtering AF 0.909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.903%

Overall 0.801% 12,928/1,614,108 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.59%	18
Finnishnot grpmax-eligible	2.17%	46
European (non-Finnish)grpmax	0.923%	108
Remaining individualsnot grpmax-eligible	0.541%	185
Ashkenazi Jewishnot grpmax-eligible	0.331%	302
African / African-American	0.121%	825
Admixed American	0.095%	1,053
South Asian	0.00549%	18,217
East Asian	0.00446%	22,438

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn36=
Coding: c.108C>T
MANE Select: NM_004937
dbSNP: rs117404824
Type: single nucleotide variant
Location: chr17:3647490 (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 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.Asn36Lys Uncertain significance ★ ⚠ 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
CTNS c.225+5G>A 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-asn36 (accessed [today's date]).

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