Is CTR9 p.Cys85Tyr (c.254G>A) pathogenic?

CTR9 p.Cys85Tyr (c.254G>A) is classified Likely pathogenic in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-01). AlphaMissense: likely pathogenic (0.9952); Very rare (popmax 0.00223%, eas); Associated with CTR9-related neurodevelopmental disorder.

What condition is associated with CTR9 p.Cys85Tyr (c.254G>A)?

CTR9 p.Cys85Tyr (c.254G>A) is associated with CTR9-related neurodevelopmental disorder (ClinVar).

How common is CTR9 p.Cys85Tyr (c.254G>A) in the general population?

CTR9 p.Cys85Tyr (c.254G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CTR9 p.Cys85Tyr (c.254G>A)?

AlphaMissense predicts likely pathogenic (score 0.9952) — an in-silico prediction, not a clinical call.

CTR9 p.Cys85Tyr

c.254G>A · rs2135356050 · VCV1173022

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9952 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTR9-related neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9952	likely pathogenic ✓ concordant with ClinVar
REVEL	0.531	indeterminate
SaProt	LLR -11.77	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 2,447 bp · p 0.00011 · regional, not allelic
Overall
CADD	25.3	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 0.00223% East Asian · 1/44,856 alleles

Overall 6.84e-05% 1/1,461,780 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.Cys85Tyr
Coding: c.254G>A
MANE Select: NM_014633
dbSNP: rs2135356050
Type: single nucleotide variant
Location: chr11:10755067 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 85: 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.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.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-cys85tyr (accessed [today's date]).

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