Is CTC1 p.Arg905fs (c.2713del) pathogenic?

CTC1 p.Arg905fs (c.2713del) is classified Likely pathogenic in CTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). Very rare (popmax 8.47e-05%, nfe); Associated with cerebroretinal microangiopathy with calcifications and cysts 1.

What condition is associated with CTC1 p.Arg905fs (c.2713del)?

CTC1 p.Arg905fs (c.2713del) is associated with cerebroretinal microangiopathy with calcifications and cysts 1 (ClinVar).

How common is CTC1 p.Arg905fs (c.2713del) in the general population?

CTC1 p.Arg905fs (c.2713del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Coats plus syndrome inherited?

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

CTC1 p.Arg905fs

c.2713del · VCV4277338

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

cerebroretinal microangiopathy with calcifications and cysts 1

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 16 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,006 alleles

Overall 6.84e-05% 1/1,461,880 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: CTC1
Protein: p.Arg905fs
Coding: c.2713del
MANE Select: NM_025099
Type: Deletion
Location: chr17:8230608 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 7 PDB
Residue 905: a β-strand

Full CTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebroretinal microangiopathy with calcifications and cysts 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Coats plus syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

CTC1 p.Arg905Pro Uncertain significance ★ ⚠ same residue
CTC1 p.Asp405fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Glu454fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.His726fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Leu1007fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Pro944fs Pathogenic ★★ same condition
CTC1 p.Pro999fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.318LE[2] Uncertain significance ★★ 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/ctc1-p-arg905fs (accessed [today's date]).

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