Is CTC1 p.Cys985del (c.2951GTT[1]) pathogenic?

CTC1 p.Cys985del (c.2951GTT[1]) is classified Pathogenic in CTC1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.04%, amr); Associated with CTC1-related disorder.

What condition is associated with CTC1 p.Cys985del (c.2951GTT[1])?

CTC1 p.Cys985del (c.2951GTT[1]) is associated with CTC1-related disorder, Coats plus syndrome, dyskeratosis congenita (ClinVar).

How common is CTC1 p.Cys985del (c.2951GTT[1]) in the general population?

CTC1 p.Cys985del (c.2951GTT[1]) is ultra-rare (popmax 0.04%, amr) (gnomAD).

CTC1 p.Cys985del

c.2951GTT[1] · rs199473679 · VCV40250

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, amr)

Conditions

CTC1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	17.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.04% Admixed American · 24/60,024 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.00192% 31/1,614,176 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.04%	2,501
African / African-American	0.00533%	18,760
Remaining individualsnot grpmax-eligible	0.0048%	20,837

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.Cys985del
Coding: c.2951GTT[1]
MANE Select: NM_025099
dbSNP: rs199473679
Type: Microsatellite
Location: chr17:8229946 (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 985: a β-strand; a UniProt-annotated variant site (in crmcc1)

Full CTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CTC1-related disorder

Also linked: Coats plus syndrome dyskeratosis congenita cerebroretinal microangiopathy with calcifications and cysts 1

Similar variants

CTC1 p.Asp44fs Likely pathogenic ★★ same condition
CTC1 p.Ser357fs Pathogenic/Likely pathogenic ★★ same condition
CTC1 p.Glu558del Uncertain significance ★★ same condition
CTC1 p.Ala605fs Pathogenic ★ same condition
CTC1 p.Arg136_Asp137insTer Pathogenic ★ same condition
CTC1 p.Arg656fs Pathogenic ★ same condition
CTC1 p.Leu597fs Pathogenic ★ same condition
CTC1 p.Trp916fs 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-cys985del (accessed [today's date]).

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