Is CTC1 p.Ala122= (c.366A>G) pathogenic?

CTC1 p.Ala122= (c.366A>G) is classified Benign/Likely benign in CTC1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 6.94%, afr) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita.

What condition is associated with CTC1 p.Ala122= (c.366A>G)?

CTC1 p.Ala122= (c.366A>G) is associated with dyskeratosis congenita, cerebroretinal microangiopathy with calcifications and cysts 1 (ClinVar).

How is Dyskeratosis congenita inherited?

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

CTC1 p.Ala122=

Q: How common is CTC1 p.Ala122= (c.366A>G) in the general population?

CTC1 p.Ala122= (c.366A>G) is common (popmax 6.94%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.366A>G · rs73244859 · VCV326087

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 6.94%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.89	GERP -5
Overall
CADD	2.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.94% African / African-American · 5,206/75,046 alleles

Filtering AF 6.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.72%

Overall 0.378% 6,101/1,614,188 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.94%	14
Admixed American	0.471%	212
Remaining individualsnot grpmax-eligible	0.462%	216
Middle Eastern	0.264%	379
South Asian	0.237%	422
East Asian	0.0646%	1,548
European (non-Finnish)	0.00525%	19,033

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.Ala122=
Coding: c.366A>G
MANE Select: NM_025099
dbSNP: rs73244859
Type: single nucleotide variant
Location: chr17:8238461 (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 122: a β-strand

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 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
CTC1 p.Arg1195Ter Pathogenic/Likely 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-ala122 (accessed [today's date]).

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