Is CTNS p.Asn323= (c.969C>T) pathogenic?

CTNS p.Asn323= (c.969C>T) is classified Conflicting classifications of pathogenicity in CTNS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-21). Rare (popmax 0.276%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Asn323= (c.969C>T)?

CTNS p.Asn323= (c.969C>T) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Asn323= (c.969C>T) in the general population?

CTNS p.Asn323= (c.969C>T) is rare (popmax 0.276%, afr) (gnomAD).

CTNS p.Asn323=

c.969C>T · rs121908128 · VCV284194

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.276%, 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 -8.2	GERP -3.1
Overall
CADD	2.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.276% African / African-American · 207/75,016 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.233%

Overall 0.0151% 243/1,611,624 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.276%	362
Admixed American	0.0267%	3,752
Remaining individualsnot grpmax-eligible	0.0176%	5,673
South Asian	0.0022%	45,520
European (non-Finnish)	0.000594%	168,333

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.Asn323=
Coding: c.969C>T
MANE Select: NM_004937
dbSNP: rs121908128
Type: single nucleotide variant
Location: chr17:3659974 (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 323: the pq-loop 2 domain; a UniProt-annotated variant site (in ctnsjan; abolished cystine transport)

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.Asn323Lys Pathogenic ★★ 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-asn323 (accessed [today's date]).

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