Is CTR9 p.Pro995Leu (c.2984C>T) pathogenic?

CTR9 p.Pro995Leu (c.2984C>T) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-30). AlphaMissense: likely benign (0.0765); Very rare (popmax 0.000255%, nfe); Associated with CTR9-related disorder.

What condition is associated with CTR9 p.Pro995Leu (c.2984C>T)?

CTR9 p.Pro995Leu (c.2984C>T) is associated with CTR9-related disorder (ClinVar).

How common is CTR9 p.Pro995Leu (c.2984C>T) in the general population?

CTR9 p.Pro995Leu (c.2984C>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CTR9 p.Pro995Leu (c.2984C>T)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

CTR9 p.Pro995Leu

c.2984C>T · VCV3779197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CTR9-related disorder

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -9.01	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 7.7	GERP 1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000255% European (non-Finnish) · 3/1,178,104 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,458,914 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.Pro995Leu
Coding: c.2984C>T
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10775522 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 995: the 'disordered' region

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

Disease context

CTR9-related disorder

Similar variants

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
CTR9 p.Tyr385Cys 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-pro995leu (accessed [today's date]).

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