Is CTR9 p.Glu735Gly (c.2204A>G) pathogenic?

CTR9 p.Glu735Gly (c.2204A>G) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: ambiguous (0.3725); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTR9 p.Glu735Gly (c.2204A>G)?

CTR9 p.Glu735Gly (c.2204A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CTR9 p.Glu735Gly (c.2204A>G) in the general population?

CTR9 p.Glu735Gly (c.2204A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTR9 p.Glu735Gly (c.2204A>G)?

AlphaMissense predicts ambiguous (score 0.3725) — an in-silico prediction, not a clinical call.

CTR9 p.Glu735Gly

c.2204A>G · rs2539386865 · VCV3078710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3725 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3725	ambiguous
REVEL	0.659	pathogenic-leaning
SaProt	LLR -10.62	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ1.00 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 2,375 bp · p 3.7e-05 · regional, not allelic
Overall
CADD	27.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTR9
Protein: p.Glu735Gly
Coding: c.2204A>G
MANE Select: NM_014633
dbSNP: rs2539386865
Type: single nucleotide variant
Location: chr11:10770304 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 735: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTR9 p.Ala644Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Ala897Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1074Trp Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1077Gln Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1163Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg725Gln Uncertain significance ★★ ⚠ same condition
CTR9 p.Asn175Ser Uncertain significance ★★ ⚠ same condition
CTR9 p.Asp1120Asn 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-glu735gly (accessed [today's date]).

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