Is CTC1 p.Ser836Pro (c.2506T>C) pathogenic?

CTC1 p.Ser836Pro (c.2506T>C) is classified Uncertain significance in CTC1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-01-16). AlphaMissense: likely benign (0.0752); Ultra-rare (popmax 0.0182%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTC1 p.Ser836Pro (c.2506T>C)?

CTC1 p.Ser836Pro (c.2506T>C) is associated with Inborn genetic diseases, dyskeratosis congenita, cerebroretinal microangiopathy with calcifications and cysts 1 (ClinVar).

How common is CTC1 p.Ser836Pro (c.2506T>C) in the general population?

CTC1 p.Ser836Pro (c.2506T>C) is ultra-rare (popmax 0.0182%, nfe) (gnomAD).

What do computational predictors say about CTC1 p.Ser836Pro (c.2506T>C)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

CTC1 p.Ser836Pro

c.2506T>C · rs62637612 · VCV326070

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.409	indeterminate
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.088 · regional, not allelic
Overall
CADD	15.97	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0182% European (non-Finnish) · 215/1,179,050 alleles

Filtering AF 0.0162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.0144% 232/1,612,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0182%	5,484
Remaining individualsnot grpmax-eligible	0.00962%	10,394
African / African-American	0.00801%	12,480
Admixed American	0.00502%	19,921
Finnishnot grpmax-eligible	0.00156%	64,030
South Asian	0.0011%	90,872

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.Ser836Pro
Coding: c.2506T>C
MANE Select: NM_025099
dbSNP: rs62637612
Type: single nucleotide variant
Location: chr17:8231439 (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 836: a β-strand

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

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

Similar variants

CTC1 p.Ser836Cys Uncertain significance ★ ⚠ same residue
CTC1 p.Ser836= Likely benign ★ 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

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-ser836pro (accessed [today's date]).

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