Is CTC1 p.Gln461= (c.1383G>A) pathogenic?

CTC1 p.Gln461= (c.1383G>A) is classified Benign/Likely benign in CTC1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.91%, nfe); Associated with cerebroretinal microangiopathy with calcifications and cysts 1.

How common is CTC1 p.Gln461= (c.1383G>A) in the general population?

CTC1 p.Gln461= (c.1383G>A) is low-frequency (popmax 1.91%, nfe) (gnomAD).

How is Coats plus syndrome inherited?

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

CTC1 p.Gln461=

Q: What condition is associated with CTC1 p.Gln461= (c.1383G>A)?

CTC1 p.Gln461= (c.1383G>A) is associated with cerebroretinal microangiopathy with calcifications and cysts 1, dyskeratosis congenita (ClinVar).

c.1383G>A · rs145192682 · VCV128859

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -0.78
Overall
CADD	5.801	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.91% European (non-Finnish) · 22,504/1,180,012 alleles

Filtering AF 1.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.88%

Overall 1.56% 25,113/1,614,190 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.91%	52
Remaining individualsnot grpmax-eligible	1.49%	67
Ashkenazi Jewishnot grpmax-eligible	1.27%	79
Finnishnot grpmax-eligible	0.918%	109
Admixed American	0.367%	273
South Asian	0.307%	325
African / African-American	0.27%	370
Middle Eastern	0.165%	606
East Asian	0.00668%	14,963

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.Gln461=
Coding: c.1383G>A
MANE Select: NM_025099
dbSNP: rs145192682
Type: single nucleotide variant
Location: chr17:8235109 (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.Gln461His 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-gln461 (accessed [today's date]).

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