Is CTC1 p.Asp330= (c.990C>T) pathogenic?

CTC1 p.Asp330= (c.990C>T) is classified Benign in CTC1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 22.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with cerebroretinal microangiopathy with calcifications and cysts 1.

How is Coats plus syndrome inherited?

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

CTC1 p.Asp330=

Q: What condition is associated with CTC1 p.Asp330= (c.990C>T)?

CTC1 p.Asp330= (c.990C>T) is associated with cerebroretinal microangiopathy with calcifications and cysts 1, dyskeratosis congenita (ClinVar).

Q: How common is CTC1 p.Asp330= (c.990C>T) in the general population?

CTC1 p.Asp330= (c.990C>T) is common (popmax 22.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.990C>T · rs74506939 · VCV128862

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 22.7%, nfe) — too common for a highly-penetrant pathogenic allele

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 -0.38	GERP -4.8
Overall
CADD	0.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.7% European (non-Finnish) · 267,824/1,179,988 alleles

Filtering AF 22.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.6%

Overall 19.8% 319,765/1,614,114 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	22.7%	4
Ashkenazi Jewishnot grpmax-eligible	22%	5
Amishnot grpmax-eligible	21%	5
Remaining individualsnot grpmax-eligible	18.4%	5
Middle Eastern	18.3%	5
Finnishnot grpmax-eligible	15.7%	6
South Asian	12.3%	8
Admixed American	11%	9
African / African-American	4.42%	23
East Asian	2.99%	33

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.Asp330=
Coding: c.990C>T
MANE Select: NM_025099
dbSNP: rs74506939
Type: single nucleotide variant
Location: chr17:8236145 (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 330: the 'disordered' region

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.Asp330Glu Uncertain significance ★ ⚠ same residue
CTC1 p.Asp330Tyr 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

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-asp330 (accessed [today's date]).

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