Is CTR9 p.Ala419Val (c.1256C>T) pathogenic?

CTR9 p.Ala419Val (c.1256C>T) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-28). AlphaMissense: likely pathogenic (0.9995); Very rare (popmax 8.47e-05%, nfe); Associated with CTR9-related neurodevelopmental disorder.

What condition is associated with CTR9 p.Ala419Val (c.1256C>T)?

CTR9 p.Ala419Val (c.1256C>T) is associated with CTR9-related neurodevelopmental disorder (ClinVar).

How common is CTR9 p.Ala419Val (c.1256C>T) in the general population?

CTR9 p.Ala419Val (c.1256C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CTR9 p.Ala419Val (c.1256C>T)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

CTR9 p.Ala419Val

c.1256C>T · VCV3600387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTR9-related neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 4% in CTR9
REVEL	0.516	indeterminate
SaProt	LLR -14.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,980 alleles

Overall 6.84e-05% 1/1,461,812 alleles · very rare

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.Ala419Val
Coding: c.1256C>T
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10764173 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 419: 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.Ala419Thr Likely benign ★ same residue
CTR9 p.Asn455Ser Likely pathogenic ★★ same condition
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

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-ala419val (accessed [today's date]).

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