Is CTC1 p.Arg561Cys (c.1681C>T) pathogenic?

CTC1 p.Arg561Cys (c.1681C>T) is classified Likely benign in CTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.0804); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with CTC1 p.Arg561Cys (c.1681C>T)?

CTC1 p.Arg561Cys (c.1681C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTC1 p.Arg561Cys (c.1681C>T) in the general population?

CTC1 p.Arg561Cys (c.1681C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CTC1 p.Arg561Cys (c.1681C>T)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

CTC1 p.Arg561Cys

c.1681C>T · rs202212634 · VCV2216977

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -10.03	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.4	GERP -3.5
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.088 · regional, not allelic
Overall
CADD	8.745	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000972%

Overall 0.00174% 28/1,610,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
East Asian	0.00446%	22,398
European (non-Finnish)	0.00178%	56,120
Admixed American	0.00169%	59,332
Remaining individualsnot grpmax-eligible	0.0016%	62,362
African / African-American	0.00134%	74,902
South Asian	0.00111%	90,380

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.Arg561Cys
Coding: c.1681C>T
MANE Select: NM_025099
dbSNP: rs202212634
Type: single nucleotide variant
Location: chr17:8234592 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTC1 p.Arg561His Uncertain significance ★★ ⚠ same residue
CTC1 p.Arg561Ser Uncertain significance ★★ ⚠ same residue
CTC1 p.Arg561Pro Uncertain significance ★ ⚠ same residue
CTC1 p.Arg561= Likely benign ★ same residue
CTC1 p.Ala1094Val Uncertain significance ★★ ⚠ same condition
CTC1 p.Ala1096Thr Uncertain significance ★★ ⚠ same condition
CTC1 p.Ala422Val Uncertain significance ★★ ⚠ same condition
CTC1 p.Ala601Thr Uncertain significance ★★ ⚠ 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-arg561cys (accessed [today's date]).

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