Is CTC1 p.Arg232Gln (c.695G>A) pathogenic?

CTC1 p.Arg232Gln (c.695G>A) is classified Benign in CTC1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.088); Low-frequency (popmax 2.86%, sas); Associated with dyskeratosis congenita.

What condition is associated with CTC1 p.Arg232Gln (c.695G>A)?

CTC1 p.Arg232Gln (c.695G>A) is associated with dyskeratosis congenita, cerebroretinal microangiopathy with calcifications and cysts 1 (ClinVar).

How common is CTC1 p.Arg232Gln (c.695G>A) in the general population?

CTC1 p.Arg232Gln (c.695G>A) is low-frequency (popmax 2.86%, sas) (gnomAD).

How is Dyskeratosis congenita inherited?

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

What do computational predictors say about CTC1 p.Arg232Gln (c.695G>A)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

CTC1 p.Arg232Gln

c.695G>A · rs201592575 · VCV210797

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.86%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.38	GERP -2.3
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.088 · regional, not allelic
Overall
CADD	14.98	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.86% South Asian · 2,606/91,056 alleles

Filtering AF 2.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.73%

Overall 0.177% 2,855/1,613,824 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.86%	35
Remaining individualsnot grpmax-eligible	0.237%	422
Middle Eastern	0.132%	758
East Asian	0.0736%	1,360
African / African-American	0.0174%	5,762
European (non-Finnish)	0.0039%	25,652
Admixed American	0.00167%	59,966

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.Arg232Gln
Coding: c.695G>A
MANE Select: NM_025099
dbSNP: rs201592575
Type: single nucleotide variant
Location: chr17:8237472 (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.Arg232Ter Pathogenic ★ 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-arg232gln (accessed [today's date]).

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