Is CTR9 p.Ser229Cys (c.686C>G) pathogenic?

CTR9 p.Ser229Cys (c.686C>G) is classified Uncertain significance in CTR9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-13). AlphaMissense: likely benign (0.1284); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTR9 p.Ser229Cys (c.686C>G)?

CTR9 p.Ser229Cys (c.686C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CTR9 p.Ser229Cys (c.686C>G) in the general population?

CTR9 p.Ser229Cys (c.686C>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CTR9 p.Ser229Cys (c.686C>G)?

AlphaMissense predicts likely benign (score 0.1284) — an in-silico prediction, not a clinical call.

CTR9 p.Ser229Cys

c.686C>G · rs994091482 · VCV2662912

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1284 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1284	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -11.96	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
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 0.74	unconstrained · MANE · 6,286 bp · p 0.0012 · regional, not allelic
Overall
CADD	27.3	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 0.000508% European (non-Finnish) · 6/1,179,946 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,878 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.Ser229Cys
Coding: c.686C>G
MANE Select: NM_014633
dbSNP: rs994091482
Type: single nucleotide variant
Location: chr11:10760266 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB

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.Ser229= 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-ser229cys (accessed [today's date]).

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