Is CTR9 p.Arg627Leu (c.1880G>T) pathogenic?

CTR9 p.Arg627Leu (c.1880G>T) is classified Uncertain significance in CTR9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.9892); Absent from gnomAD v4.1; Associated with CTR9-related disorder.

What condition is associated with CTR9 p.Arg627Leu (c.1880G>T)?

CTR9 p.Arg627Leu (c.1880G>T) is associated with CTR9-related disorder (ClinVar).

How common is CTR9 p.Arg627Leu (c.1880G>T) in the general population?

CTR9 p.Arg627Leu (c.1880G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTR9 p.Arg627Leu (c.1880G>T)?

AlphaMissense predicts likely pathogenic (score 0.9892) — an in-silico prediction, not a clinical call.

CTR9 p.Arg627Leu

c.1880G>T · VCV3346209

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9892 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTR9-related disorder

Computational evidence

Protein change
AlphaMissense	0.9892	likely pathogenic
REVEL	0.448	indeterminate
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 5,532 bp · p 3.5e-22 · regional, not allelic
Overall
CADD	25.1	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

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.Arg627Leu
Coding: c.1880G>T
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10768081 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 627: an α-helix

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

Disease context

CTR9-related disorder

Similar variants

CTR9 p.Arg627Cys Uncertain significance ★ ⚠ same residue
CTR9 c.1960+3G>A Uncertain significance ★★ same condition
CTR9 c.45+5G>T Uncertain significance ★★ same condition
CTR9 p.Ala370Thr Uncertain significance ★★ ⚠ same condition
CTR9 p.Ala567Ser Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1095Lys Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1122His Uncertain significance ★★ ⚠ same condition
CTR9 p.Lys282Arg 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-arg627leu (accessed [today's date]).

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