Is CTC1 p.Leu63= (c.189C>G) pathogenic?

CTC1 p.Leu63= (c.189C>G) is classified Benign/Likely benign in CTC1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). Rare (popmax 0.754%, eas); Associated with dyskeratosis congenita.

What condition is associated with CTC1 p.Leu63= (c.189C>G)?

CTC1 p.Leu63= (c.189C>G) is associated with dyskeratosis congenita, cerebroretinal microangiopathy with calcifications and cysts 1 (ClinVar).

How common is CTC1 p.Leu63= (c.189C>G) in the general population?

CTC1 p.Leu63= (c.189C>G) is rare (popmax 0.754%, eas) (gnomAD).

How is Dyskeratosis congenita inherited?

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

CTC1 p.Leu63=

c.189C>G · rs188658691 · VCV326088

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.754%, eas)

Conditions

dyskeratosis congenita

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 2.2	GERP 1.8, phastCons 1
Overall
CADD	7.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.754% East Asian · 338/44,820 alleles

Filtering AF 0.688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.662%

Overall 0.0445% 718/1,611,800 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.754%	133
Ashkenazi Jewishnot grpmax-eligible	0.227%	440
Finnishnot grpmax-eligible	0.188%	533
Middle Eastern	0.0673%	1,486
South Asian	0.0497%	2,014
Remaining individualsnot grpmax-eligible	0.0481%	2,081
European (non-Finnish)	0.00958%	10,434
African / African-American	0.00133%	74,932

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.Leu63=
Coding: c.189C>G
MANE Select: NM_025099
dbSNP: rs188658691
Type: single nucleotide variant
Location: chr17:8242993 (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

dyskeratosis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cerebroretinal microangiopathy with calcifications and cysts 1

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

CTC1 p.Leu63Phe 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-leu63 (accessed [today's date]).

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