Is CTR9 p.Tyr385Cys (c.1154A>G) pathogenic?

CTR9 p.Tyr385Cys (c.1154A>G) is classified Uncertain significance in CTR9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.756); Ultra-rare (popmax 0.0334%, amr); Associated with Predisposition to Wilms tumor.

What condition is associated with CTR9 p.Tyr385Cys (c.1154A>G)?

CTR9 p.Tyr385Cys (c.1154A>G) is associated with Predisposition to Wilms tumor (ClinVar).

How common is CTR9 p.Tyr385Cys (c.1154A>G) in the general population?

CTR9 p.Tyr385Cys (c.1154A>G) is ultra-rare (popmax 0.0334%, amr) (gnomAD).

What do computational predictors say about CTR9 p.Tyr385Cys (c.1154A>G)?

AlphaMissense predicts likely pathogenic (score 0.756) — an in-silico prediction, not a clinical call.

CTR9 p.Tyr385Cys

c.1154A>G · rs202173615 · VCV3078709

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Predisposition to Wilms tumor

Computational evidence

Protein change
AlphaMissense	0.756	likely pathogenic
REVEL	0.562	indeterminate
SaProt	LLR -10.70	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 1,051 bp · p 1.2e-12 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0334% Admixed American · 20/59,792 alleles

Filtering AF 0.0222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0185%

Overall 0.00192% 31/1,612,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0334%	2,990
Remaining individualsnot grpmax-eligible	0.00641%	15,611
East Asian	0.00223%	44,874
African / African-American	0.00134%	74,838
European (non-Finnish)	0.000424%	235,956

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.Tyr385Cys
Coding: c.1154A>G
MANE Select: NM_014633
dbSNP: rs202173615
Type: single nucleotide variant
Location: chr11:10763839 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 385: an α-helix

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 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.Arg1122His Uncertain significance ★★ ⚠ same condition
CTR9 p.Lys282Arg 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-tyr385cys (accessed [today's date]).

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