Is CTNS p.Phe247fs (c.741del) pathogenic?

CTNS p.Phe247fs (c.741del) is classified Pathogenic in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). Very rare (popmax 0.00136%, nfe); Associated with cystinosis.

What condition is associated with CTNS p.Phe247fs (c.741del)?

CTNS p.Phe247fs (c.741del) is associated with cystinosis (ClinVar).

How common is CTNS p.Phe247fs (c.741del) in the general population?

CTNS p.Phe247fs (c.741del) is very rare (popmax 0.00136%, nfe) (gnomAD).

How is Cystinosis inherited?

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

CTNS p.Phe247fs

c.741del · rs756182448 · VCV2577044

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

cystinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,966 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.0011% 16/1,459,828 alleles · very rare

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.Phe247fs
Coding: c.741del
MANE Select: NM_004937
dbSNP: rs756182448
Type: Deletion
Location: chr17:3658064 (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 247: an α-helix

Full CTNS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cystinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cystinosis (Orphanet):

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

Similar variants

CTNS c.559_561+24del Pathogenic/Likely pathogenic ★★ same condition
CTNS c.561+1del Pathogenic/Likely pathogenic ★★ same condition
CTNS c.61_61+2del Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Gln108fs Pathogenic ★★ same condition
CTNS p.Gly258fs Pathogenic ★★ same condition
CTNS p.Ile343_Asp346del Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Ser270del Pathogenic/Likely pathogenic ★★ same condition
CTNS p.Thr251fs 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-phe247fs (accessed [today's date]).

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