Is CTR9 p.Arg1122His (c.3365G>A) pathogenic?

CTR9 p.Arg1122His (c.3365G>A) is classified Uncertain significance in CTR9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-05). AlphaMissense: likely benign (0.0766); Ultra-rare (popmax 0.024%, afr); Associated with Predisposition to Wilms tumor.

What condition is associated with CTR9 p.Arg1122His (c.3365G>A)?

CTR9 p.Arg1122His (c.3365G>A) is associated with Predisposition to Wilms tumor (ClinVar).

How common is CTR9 p.Arg1122His (c.3365G>A) in the general population?

CTR9 p.Arg1122His (c.3365G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about CTR9 p.Arg1122His (c.3365G>A)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

CTR9 p.Arg1122His

c.3365G>A · rs367908001 · VCV1403672

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Predisposition to Wilms tumor

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.85, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	21.9	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 0.024% African / African-American · 18/74,890 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00167% 27/1,613,982 alleles · ultra-rare exomes 20/1,461,886 · genomes 7/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,161
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Finnishnot grpmax-eligible	0.00312%	32,002
Admixed American	0.00167%	59,990
European (non-Finnish)	0.000339%	295,010

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
Protein: p.Arg1122His
Coding: c.3365G>A
MANE Select: NM_014633
dbSNP: rs367908001
Type: single nucleotide variant
Location: chr11:10778948 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 1122: the 'disordered' region

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

Disease context

Predisposition to Wilms tumor

Similar variants

CTR9 p.Arg1122Cys Uncertain significance ★ ⚠ same residue
CTR9 p.Arg1122Pro Uncertain significance ★ ⚠ same residue
CTR9 c.1960+3G>A Uncertain significance ★★ same condition
CTR9 c.45+5G>T 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.Lys282Arg 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-p-arg1122his (accessed [today's date]).

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