Is CTR9 p.Glu1069Lys (c.3205G>A) pathogenic?

CTR9 p.Glu1069Lys (c.3205G>A) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). AlphaMissense: likely benign (0.123); Ultra-rare (popmax 0.0173%, afr).

How common is CTR9 p.Glu1069Lys (c.3205G>A) in the general population?

CTR9 p.Glu1069Lys (c.3205G>A) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about CTR9 p.Glu1069Lys (c.3205G>A)?

AlphaMissense predicts likely benign (score 0.123) — an in-silico prediction, not a clinical call.

CTR9 p.Glu1069Lys

c.3205G>A · rs150955197 · VCV2084703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.123 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.123	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -10.48	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.0173% African / African-American · 13/75,054 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00136% 22/1,614,208 alleles · ultra-rare exomes 14/1,461,890 · genomes 8/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,773
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.00167%	60,026
European (non-Finnish)	0.000254%	393,345

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.Glu1069Lys
Coding: c.3205G>A
MANE Select: NM_014633
dbSNP: rs150955197
Type: single nucleotide variant
Location: chr11:10778788 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 1069: the 'disordered' region

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

Similar variants

CTR9 p.Asn455Ser Likely pathogenic ★★ same type
CTR9 p.Ile17Thr Pathogenic/Likely pathogenic ★★ same type
CTR9 p.Pro25Arg Pathogenic/Likely pathogenic ★★ same type
CTR9 c.1960+3G>A Uncertain significance ★★ same type
CTR9 c.2109+4A>G Uncertain significance ★★ same type
CTR9 c.2445-3T>C Uncertain significance ★★ same type
CTR9 c.45+5G>T Uncertain significance ★★ same type
CTR9 c.593-8T>A Uncertain significance ★★ same type

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-glu1069lys (accessed [today's date]).

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