Is CTR9 p.Ser1041Thr (c.3122G>C) pathogenic?

CTR9 p.Ser1041Thr (c.3122G>C) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.0703); Very rare (popmax 0.00769%, sas); Associated with Inborn genetic diseases.

What condition is associated with CTR9 p.Ser1041Thr (c.3122G>C)?

CTR9 p.Ser1041Thr (c.3122G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTR9 p.Ser1041Thr (c.3122G>C) in the general population?

CTR9 p.Ser1041Thr (c.3122G>C) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about CTR9 p.Ser1041Thr (c.3122G>C)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CTR9 p.Ser1041Thr

c.3122G>C · VCV4008095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -9.21	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 9.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	23.7	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 0.00769% South Asian · 7/91,008 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000479% 7/1,460,684 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.Ser1041Thr
Coding: c.3122G>C
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10778705 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 1041: the 'disordered' region; a modified residue (phosphoserine)

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.Ser1041= 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-ser1041thr (accessed [today's date]).

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