Is CTR9 p.Pro1153Ser (c.3457C>T) pathogenic?

CTR9 p.Pro1153Ser (c.3457C>T) is classified Likely benign in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-22). AlphaMissense: likely benign (0.074); Absent from gnomAD v4.1; Associated with complex neurodevelopmental disorder.

What condition is associated with CTR9 p.Pro1153Ser (c.3457C>T)?

CTR9 p.Pro1153Ser (c.3457C>T) is associated with complex neurodevelopmental disorder (ClinVar).

How common is CTR9 p.Pro1153Ser (c.3457C>T) in the general population?

CTR9 p.Pro1153Ser (c.3457C>T) is absent from gnomAD v4.1 (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CTR9 p.Pro1153Ser (c.3457C>T)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

CTR9 p.Pro1153Ser

c.3457C>T · VCV4852325

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complex neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.80	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 2.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	21.0	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

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.Pro1153Ser
Coding: c.3457C>T
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10779040 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 1153: the 'disordered' region

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

Disease context

complex neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

Similar variants

CTR9 p.Pro1153= Likely benign ★ same residue
CTR9 p.Asn455Ser Likely pathogenic ★★ same type
CTR9 p.Ile17Thr Pathogenic/Likely pathogenic ★★ same type
CTR9 p.Pro25Arg Pathogenic/Likely pathogenic ★★ same type
CTR9 c.1960+3G>A Uncertain significance ★★ same type
CTR9 c.2109+4A>G Uncertain significance ★★ same type
CTR9 c.2445-3T>C Uncertain significance ★★ same type
CTR9 c.45+5G>T Uncertain significance ★★ same type

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-pro1153ser (accessed [today's date]).

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