Is CTR9 p.Ala567Ser (c.1699G>T) pathogenic?

CTR9 p.Ala567Ser (c.1699G>T) is classified Uncertain significance in CTR9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-11). AlphaMissense: ambiguous (0.4322); Very rare (popmax 0.000339%, nfe); Associated with Predisposition to Wilms tumor.

What condition is associated with CTR9 p.Ala567Ser (c.1699G>T)?

CTR9 p.Ala567Ser (c.1699G>T) is associated with Predisposition to Wilms tumor (ClinVar).

How common is CTR9 p.Ala567Ser (c.1699G>T) in the general population?

CTR9 p.Ala567Ser (c.1699G>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CTR9 p.Ala567Ser (c.1699G>T)?

AlphaMissense predicts ambiguous (score 0.4322) — an in-silico prediction, not a clinical call.

CTR9 p.Ala567Ser

c.1699G>T · VCV3713156

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4322 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Predisposition to Wilms tumor

Computational evidence

Protein change
AlphaMissense	0.4322	ambiguous
REVEL	0.337	indeterminate
SaProt	LLR -8.88	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 5,532 bp · p 3.5e-22 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,954 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000558% 9/1,613,888 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00625%	16,004
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)grpmax	0.000339%	294,989

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala567Ser
Coding: c.1699G>T
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10767818 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 567: 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 p.Ala567Pro 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.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

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-ala567ser (accessed [today's date]).

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