Is CTC1 p.Arg987Trp (c.2959C>T) pathogenic?

CTC1 p.Arg987Trp (c.2959C>T) is classified Pathogenic/Likely pathogenic in CTC1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-09-08). AlphaMissense: likely benign (0.1298); Ultra-rare (popmax 0.0127%, nfe); Associated with CTC1-related disorder.

What condition is associated with CTC1 p.Arg987Trp (c.2959C>T)?

CTC1 p.Arg987Trp (c.2959C>T) is associated with CTC1-related disorder, dyskeratosis congenita, cerebroretinal microangiopathy with calcifications and cysts 1 (ClinVar).

How common is CTC1 p.Arg987Trp (c.2959C>T) in the general population?

CTC1 p.Arg987Trp (c.2959C>T) is ultra-rare (popmax 0.0127%, nfe) (gnomAD).

What do computational predictors say about CTC1 p.Arg987Trp (c.2959C>T)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

CTC1 p.Arg987Trp

c.2959C>T · rs202138550 · VCV30996

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0127%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign ⚠ discordant with ClinVar
REVEL	0.606	indeterminate
SaProt	LLR -9.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.23	acceptor loss · deltas
Pangolin	Δ0.30	loss · gain 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 0.86, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.088 · regional, not allelic
Overall
CADD	29.7	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 0.0127% European (non-Finnish) · 150/1,180,004 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.00991% 160/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0127%	7,867
Admixed American	0.00333%	30,003
South Asian	0.00329%	30,359
African / African-American	0.00267%	37,509
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,508
Finnishnot grpmax-eligible	0.00156%	64,006

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.Arg987Trp
Coding: c.2959C>T
MANE Select: NM_025099
dbSNP: rs202138550
Type: single nucleotide variant
Location: chr17:8229943 (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 987: 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: dyskeratosis congenita cerebroretinal microangiopathy with calcifications and cysts 1

Similar variants

CTC1 p.Arg987Gln Likely 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-arg987trp (accessed [today's date]).

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