Is CTR9 p.Arg910His (c.2729G>A) pathogenic?

CTR9 p.Arg910His (c.2729G>A) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: ambiguous (0.3414); Very rare (popmax 0.00447%, eas); Associated with Predisposition to Wilms tumor.

What condition is associated with CTR9 p.Arg910His (c.2729G>A)?

CTR9 p.Arg910His (c.2729G>A) is associated with Predisposition to Wilms tumor (ClinVar).

How common is CTR9 p.Arg910His (c.2729G>A) in the general population?

CTR9 p.Arg910His (c.2729G>A) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about CTR9 p.Arg910His (c.2729G>A)?

AlphaMissense predicts ambiguous (score 0.3414) — an in-silico prediction, not a clinical call.

CTR9 p.Arg910His

c.2729G>A · rs764521025 · VCV1710948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3414 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Predisposition to Wilms tumor

Computational evidence

Protein change
AlphaMissense	0.3414	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -9.38	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	34.0	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 0.00447% East Asian · 2/44,758 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000808% 13/1,608,226 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,379
African / African-American	0.00269%	37,232
European (non-Finnish)	0.000764%	130,815

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.Arg910His
Coding: c.2729G>A
MANE Select: NM_014633
dbSNP: rs764521025
Type: single nucleotide variant
Location: chr11:10774013 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 910: 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.Arg910Cys 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.Arg1122His 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-arg910his (accessed [today's date]).

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