Is CTC1 p.Leu1007fs (c.3019del) pathogenic?

CTC1 p.Leu1007fs (c.3019del) is classified Pathogenic/Likely pathogenic in CTC1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-03-26). Ultra-rare (popmax 0.0169%, nfe); Associated with retinal disorder.

What condition is associated with CTC1 p.Leu1007fs (c.3019del)?

CTC1 p.Leu1007fs (c.3019del) is associated with retinal disorder, Coats plus syndrome, dyskeratosis congenita (ClinVar).

How common is CTC1 p.Leu1007fs (c.3019del) in the general population?

CTC1 p.Leu1007fs (c.3019del) is ultra-rare (popmax 0.0169%, nfe) (gnomAD).

CTC1 p.Leu1007fs

c.3019del · rs199473680 · VCV843472

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, nfe)

Conditions

retinal disorder

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 19 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 0.75, phastCons 1
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% European (non-Finnish) · 199/1,179,180 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.0161% 260/1,613,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0828%	1,208
European (non-Finnish)grpmax	0.0169%	5,926
Remaining individualsnot grpmax-eligible	0.00961%	10,408
African / African-American	0.00267%	37,467

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu1007fs
Coding: c.3019del
MANE Select: NM_025099
dbSNP: rs199473680
Type: Deletion
Location: chr17:8229439 (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 1007: an α-helix

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

Disease context

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

Also linked: Coats plus syndrome dyskeratosis congenita cerebroretinal microangiopathy with calcifications and cysts 1

Similar variants

CTC1 p.Asp405fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Glu454fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Glu557fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.His726fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Pro944fs Pathogenic ★★ same condition
CTC1 p.Pro999fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Ser583fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Val854fs Pathogenic/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/ctc1-p-leu1007fs (accessed [today's date]).

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