Is CTNS p.Asp74= (c.222T>C) pathogenic?

CTNS p.Asp74= (c.222T>C) is classified Likely benign in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). Absent from gnomAD v4.1; Associated with ocular cystinosis.

What condition is associated with CTNS p.Asp74= (c.222T>C)?

CTNS p.Asp74= (c.222T>C) is associated with ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Asp74= (c.222T>C) in the general population?

CTNS p.Asp74= (c.222T>C) 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.Asp74=

c.222T>C · rs1597624144 · VCV1112075

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ocular cystinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.051	GERP -3.4, phastCons 0.9
Overall
CADD	6.968	PHRED · no single calibrated threshold — expert panels disagree

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.Asp74=
Coding: c.222T>C
MANE Select: NM_004937
dbSNP: rs1597624144
Type: single nucleotide variant
Location: chr17:3648928 (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

For Cystinosis (Orphanet):

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

Similar variants

CTNS p.Asp74Gly Uncertain significance ★★ ⚠ same residue
CTNS p.Asp74Asn Likely benign ★★ 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

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-asp74 (accessed [today's date]).

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