Is CTR9 c.45+5G>T pathogenic?

CTR9 c.45+5G>T is classified Uncertain significance in CTR9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-07). Very rare (popmax 0.0089%, nfe); Associated with Predisposition to Wilms tumor.

What condition is associated with CTR9 c.45+5G>T?

CTR9 c.45+5G>T is associated with Predisposition to Wilms tumor (ClinVar).

How common is CTR9 c.45+5G>T in the general population?

CTR9 c.45+5G>T is very rare (popmax 0.0089%, nfe) (gnomAD).

CTR9 c.45+5G>T

rs758205417 · VCV1447960

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0089%, nfe)

Conditions

Predisposition to Wilms tumor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP -1.2, phastCons 1
Non-coding constraint	Z 2.43	1 kb window · o/e 0.79 · regional · uncalibrated
Overall
CADD	19.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0089% European (non-Finnish) · 105/1,179,996 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00675% 109/1,613,882 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0089%	11,238
Remaining individualsnot grpmax-eligible	0.0048%	20,836
African / African-American	0.00133%	75,060

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: CTR9
Coding: c.45+5G>T
MANE Select: NM_014633
dbSNP: rs758205417
Type: single nucleotide variant
Location: chr11:10751462 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB

Full CTR9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Predisposition to Wilms tumor

Similar variants

CTR9 c.1960+3G>A Uncertain significance ★★ same condition
CTR9 p.Ala370Thr Uncertain significance ★★ ⚠ same condition
CTR9 p.Ala567Ser Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1095Lys Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1122His Uncertain significance ★★ ⚠ same condition
CTR9 p.Lys282Arg Uncertain significance ★★ ⚠ same condition
CTR9 p.Tyr385Cys Uncertain significance ★★ ⚠ same condition
CTR9 p.Tyr712Cys 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/ctr9-c-45-plus-5g-t (accessed [today's date]).

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