Is CTR9 p.Leu851Val (c.2551C>G) pathogenic?

CTR9 p.Leu851Val (c.2551C>G) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0202%, sas); Associated with Inborn genetic diseases.

What condition is associated with CTR9 p.Leu851Val (c.2551C>G)?

CTR9 p.Leu851Val (c.2551C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CTR9 p.Leu851Val (c.2551C>G) in the general population?

CTR9 p.Leu851Val (c.2551C>G) is ultra-rare (popmax 0.0202%, sas) (gnomAD).

What do computational predictors say about CTR9 p.Leu851Val (c.2551C>G)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

CTR9 p.Leu851Val

c.2551C>G · VCV4008096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -7.38	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 2.2	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	19.84	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 0.0202% South Asian · 18/89,164 alleles

Filtering AF 0.013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.00145% 21/1,450,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0202%	4,954
Middle Eastern	0.0167%	6,000
Remaining individualsnot grpmax-eligible	0.00161%	61,990
European (non-Finnish)	8.5e-05%	1,176,376

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.Leu851Val
Coding: c.2551C>G
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10772626 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 851: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTR9 p.Leu851= Likely benign ★ same residue
CTR9 p.Ala644Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Ala897Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1074Trp Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1077Gln Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1163Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg725Gln Uncertain significance ★★ ⚠ same condition
CTR9 p.Asn175Ser 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-leu851val (accessed [today's date]).

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