Is CTR9 p.Cys1052Arg (c.3154T>C) pathogenic?

CTR9 p.Cys1052Arg (c.3154T>C) is classified Benign in CTR9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.0618); Low-frequency (popmax 3.79%, afr).

How common is CTR9 p.Cys1052Arg (c.3154T>C) in the general population?

CTR9 p.Cys1052Arg (c.3154T>C) is low-frequency (popmax 3.79%, afr) (gnomAD).

What do computational predictors say about CTR9 p.Cys1052Arg (c.3154T>C)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

CTR9 p.Cys1052Arg

c.3154T>C · rs35696189 · VCV1165526

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.79%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -0.32	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 2.1	GERP 0.018, phastCons 0.027
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	8.031	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 3.79% African / African-American · 2,841/74,980 alleles

Filtering AF 3.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.63%

Overall 0.2% 3,222/1,614,038 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.79%	26
Admixed American	0.273%	366
Remaining individualsnot grpmax-eligible	0.262%	381
Middle Eastern	0.066%	1,515
European (non-Finnish)	0.0039%	25,652
South Asian	0.00329%	30,355

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.Cys1052Arg
Coding: c.3154T>C
MANE Select: NM_014633
dbSNP: rs35696189
Type: single nucleotide variant
Location: chr11:10778737 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 1052: 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-cys1052arg (accessed [today's date]).

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