Is CTNS p.Pro111= (c.333G>A) pathogenic?

CTNS p.Pro111= (c.333G>A) is classified Likely benign in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Pro111= (c.333G>A)?

CTNS p.Pro111= (c.333G>A) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Pro111= (c.333G>A) in the general population?

CTNS p.Pro111= (c.333G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CTNS p.Pro111=

c.333G>A · rs755169805 · VCV1146556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.3	GERP -3.7
Overall
CADD	6.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000479% 7/1,461,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.00267%	37,519
European (non-Finnish)	0.000339%	295,006

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.Pro111=
Coding: c.333G>A
MANE Select: NM_004937
dbSNP: rs755169805
Type: single nucleotide variant
Location: chr17:3655224 (GRCh38)

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

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-pro111 (accessed [today's date]).

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