Is CTC1 p.Ser357fs (c.1070_1074del) pathogenic?

CTC1 p.Ser357fs (c.10701074del) is classified Pathogenic/Likely pathogenic in CTC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-27). Ultra-rare (popmax 0.0165%, sas); Associated with cerebroretinal microangiopathy with calcifications and cysts 1.

How common is CTC1 p.Ser357fs (c.1070_1074del) in the general population?

CTC1 p.Ser357fs (c.1070_1074del) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

How is Coats plus syndrome inherited?

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

CTC1 p.Ser357fs

Q: What condition is associated with CTC1 p.Ser357fs (c.1070_1074del)?

CTC1 p.Ser357fs (c.1070_1074del) is associated with cerebroretinal microangiopathy with calcifications and cysts 1, dyskeratosis congenita (ClinVar).

c.1070_1074del · rs773120259 · VCV862044

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

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 6 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.32	GERP -4.8
Overall
CADD	26.6	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 0.0165% South Asian · 15/91,036 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00323% 52/1,611,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,069
Remaining individualsnot grpmax-eligible	0.00481%	20,793
African / African-American	0.00401%	24,953
European (non-Finnish)	0.00263%	37,990

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.Ser357fs
Coding: c.1070_1074del
MANE Select: NM_025099
dbSNP: rs773120259
Type: Microsatellite
Location: chr17:8236061 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 7 PDB

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

Also linked: dyskeratosis congenita

For Coats plus syndrome (Orphanet):

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

Similar variants

CTC1 p.Asp44fs Likely pathogenic ★★ same condition
CTC1 p.Cys985del Pathogenic ★★ same condition
CTC1 p.Glu558del Uncertain significance ★★ same condition
CTC1 p.Ala605fs Pathogenic ★ same condition
CTC1 p.Arg136_Asp137insTer Pathogenic ★ same condition
CTC1 p.Arg656fs Pathogenic ★ same condition
CTC1 p.Leu597fs Pathogenic ★ same condition
CTC1 c.1819-7_1819-5del 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-ser357fs (accessed [today's date]).

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