Is CTC1 p.Arg522= (c.1564C>A) pathogenic?

CTC1 p.Arg522= (c.1564C>A) is classified Likely benign in CTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Very rare (popmax 0.00267%, afr); Associated with dyskeratosis congenita.

What condition is associated with CTC1 p.Arg522= (c.1564C>A)?

CTC1 p.Arg522= (c.1564C>A) is associated with dyskeratosis congenita (ClinVar).

How common is CTC1 p.Arg522= (c.1564C>A) in the general population?

CTC1 p.Arg522= (c.1564C>A) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

CTC1 p.Arg522=

c.1564C>A · rs199698527 · VCV1158364

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 8.6	GERP 1.4, phastCons 1
Overall
CADD	9.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,826 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,611,874 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,413
European (non-Finnish)	0.00017%	589,504

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.Arg522=
Coding: c.1564C>A
MANE Select: NM_025099
dbSNP: rs199698527
Type: single nucleotide variant
Location: chr17:8234802 (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 522: an α-helix

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.Arg522Gln Uncertain significance ★★ ⚠ same residue
CTC1 p.Arg522Gly Uncertain significance ★ same residue
CTC1 p.Arg522Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
CTC1 p.Arg522Leu 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

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-arg522 (accessed [today's date]).

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