Is CTC1 p.Arg396Ter (c.1186C>T) pathogenic?

CTC1 p.Arg396Ter (c.1186C>T) is classified Pathogenic/Likely pathogenic in CTC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-18). Very rare (popmax 0.00501%, amr); Associated with cerebroretinal microangiopathy with calcifications and cysts 1.

How common is CTC1 p.Arg396Ter (c.1186C>T) in the general population?

CTC1 p.Arg396Ter (c.1186C>T) is very rare (popmax 0.00501%, amr) (gnomAD).

How is Coats plus syndrome inherited?

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

CTC1 p.Arg396Ter

Q: What condition is associated with CTC1 p.Arg396Ter (c.1186C>T)?

CTC1 p.Arg396Ter (c.1186C>T) is associated with cerebroretinal microangiopathy with calcifications and cysts 1, dyskeratosis congenita (ClinVar).

c.1186C>T · rs764019241 · VCV576930

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 23
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.73, phastCons 1
Overall
CADD	37.0	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 0.00501% Admixed American · 3/59,896 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000496% 8/1,612,342 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,965
Remaining individualsnot grpmax-eligible	0.0016%	62,392
African / African-American	0.00134%	74,836
European (non-Finnish)	0.000254%	392,946

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.Arg396Ter
Coding: c.1186C>T
MANE Select: NM_025099
dbSNP: rs764019241
Type: single nucleotide variant
Location: chr17:8235851 (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.Arg396Gln Uncertain significance ★ ⚠ same residue
CTC1 c.1617+5G>T Pathogenic/Likely pathogenic ★★ same condition
CTC1 c.1818+1G>A Likely pathogenic ★★ same condition
CTC1 c.2386-1G>A Likely pathogenic ★★ same condition
CTC1 c.2758+1G>T Pathogenic/Likely pathogenic ★★ same condition
CTC1 c.3221+1G>A Likely pathogenic ★★ same condition
CTC1 p.Ala227Val Pathogenic ★★ ⚠ same condition
CTC1 p.Arg108Ter 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-arg396ter (accessed [today's date]).

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