Is CTR9 p.Asn455Ser (c.1364A>G) pathogenic?

CTR9 p.Asn455Ser (c.1364A>G) is classified Likely pathogenic in CTR9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-09). AlphaMissense: likely pathogenic (0.7668); Very rare (popmax 0.0011%, sas); Associated with CTR9-related neurodevelopmental disorder.

What condition is associated with CTR9 p.Asn455Ser (c.1364A>G)?

CTR9 p.Asn455Ser (c.1364A>G) is associated with CTR9-related neurodevelopmental disorder (ClinVar).

How common is CTR9 p.Asn455Ser (c.1364A>G) in the general population?

CTR9 p.Asn455Ser (c.1364A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CTR9 p.Asn455Ser (c.1364A>G)?

AlphaMissense predicts likely pathogenic (score 0.7668) — an in-silico prediction, not a clinical call.

CTR9 p.Asn455Ser

c.1364A>G · rs772196842 · VCV1173024

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CTR9-related neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.7668	likely pathogenic ✓ concordant with ClinVar
REVEL	0.645	pathogenic-leaning
SaProt	LLR -10.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 1,051 bp · p 1.2e-12 · regional, not allelic
Overall
CADD	26.1	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 0.0011% South Asian · 1/91,080 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,846 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	0.000508%	196,669

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.Asn455Ser
Coding: c.1364A>G
MANE Select: NM_014633
dbSNP: rs772196842
Type: single nucleotide variant
Location: chr11:10764387 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 455: an α-helix

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

Disease context

CTR9-related neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTR9 p.Ile17Thr Pathogenic/Likely pathogenic ★★ same condition
CTR9 p.Pro25Arg Pathogenic/Likely pathogenic ★★ same condition
CTR9 c.46-1G>T Pathogenic ★ same condition
CTR9 p.Arg878Gln Likely pathogenic ★ ⚠ same condition
CTR9 p.Cys85Tyr Likely pathogenic ★ same condition
CTR9 p.Glu15Lys Likely pathogenic ★ same condition
CTR9 p.Glu26Gln Likely pathogenic ★ ⚠ same condition
CTR9 p.Glu37Gln Likely pathogenic ★ ⚠ 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-asn455ser (accessed [today's date]).

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