Is CTR9 p.Arg1095Lys (c.3284G>A) pathogenic?

CTR9 p.Arg1095Lys (c.3284G>A) is classified Uncertain significance in CTR9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0708); Ultra-rare (popmax 0.035%, amr); Associated with Predisposition to Wilms tumor, CTR9-related.

What condition is associated with CTR9 p.Arg1095Lys (c.3284G>A)?

CTR9 p.Arg1095Lys (c.3284G>A) is associated with Predisposition to Wilms tumor, CTR9-related (ClinVar).

How common is CTR9 p.Arg1095Lys (c.3284G>A) in the general population?

CTR9 p.Arg1095Lys (c.3284G>A) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about CTR9 p.Arg1095Lys (c.3284G>A)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

CTR9 p.Arg1095Lys

c.3284G>A · rs141434094 · VCV941909

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Predisposition to Wilms tumor, CTR9-related

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -7.08	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 9.9	GERP 0.86, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	22.0	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 0.035% Admixed American · 21/60,022 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0212%

Overall 0.0199% 321/1,614,232 alleles · ultra-rare exomes 286/1,461,890 · genomes 35/152,342 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,858
European (non-Finnish)	0.0245%	4,083
Remaining individualsnot grpmax-eligible	0.0144%	6,946
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00156%	64,046

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.Arg1095Lys
Coding: c.3284G>A
MANE Select: NM_014633
dbSNP: rs141434094
Type: single nucleotide variant
Location: chr11:10778867 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 1095: the 'disordered' region

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

Disease context

Predisposition to Wilms tumor, CTR9-related

Similar variants

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.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-p-arg1095lys (accessed [today's date]).

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