Is CTC1 p.Arg542fs (c.1623_1624del) pathogenic?

CTC1 p.Arg542fs (c.16231624del) is classified Pathogenic in CTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-28). Very rare (popmax 6.86e-05%); Associated with dyskeratosis congenita.

What condition is associated with CTC1 p.Arg542fs (c.1623_1624del)?

CTC1 p.Arg542fs (c.1623_1624del) is associated with dyskeratosis congenita (ClinVar).

How common is CTC1 p.Arg542fs (c.1623_1624del) in the general population?

CTC1 p.Arg542fs (c.1623_1624del) is very rare (popmax 6.86e-05%) (gnomAD).

How is Dyskeratosis congenita inherited?

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

CTC1 p.Arg542fs

c.1623_1624del · rs1567607653 · VCV2043467

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.86e-05%)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.32	GERP -2.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.86e-05%

Overall 6.86e-05% 1/1,458,232 alleles · very rare

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.Arg542fs
Coding: c.1623_1624del
MANE Select: NM_025099
dbSNP: rs1567607653
Type: Deletion
Location: chr17:8234649 (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

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.Arg542Gln Uncertain significance ★★ ⚠ same residue
CTC1 p.Arg542Pro Uncertain significance ★ ⚠ same residue
CTC1 p.Arg542Trp Uncertain significance ★ ⚠ same residue
CTC1 p.Arg542= Likely benign ★ same residue
CTC1 p.Asp405fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Glu454fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Glu557fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.His726fs 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-arg542fs (accessed [today's date]).

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