Is CTR9 p.Arg910Cys (c.2728C>T) pathogenic?

CTR9 p.Arg910Cys (c.2728C>T) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-05). AlphaMissense: likely pathogenic (0.6003); Very rare (popmax 0.00671%, eas).

How common is CTR9 p.Arg910Cys (c.2728C>T) in the general population?

CTR9 p.Arg910Cys (c.2728C>T) is very rare (popmax 0.00671%, eas) (gnomAD).

What do computational predictors say about CTR9 p.Arg910Cys (c.2728C>T)?

AlphaMissense predicts likely pathogenic (score 0.6003) — an in-silico prediction, not a clinical call.

CTR9 p.Arg910Cys

c.2728C>T · rs761302085 · VCV2171815

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6003 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00671%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6003	likely pathogenic
REVEL	0.153	moderately benign-leaning
SaProt	LLR -12.69	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	34.0	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 0.00671% East Asian · 3/44,682 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000894%

Overall 0.00081% 13/1,605,282 alleles · very rare exomes 11/1,453,486 · genomes 2/151,796 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00671%	14,894
African / African-American	0.00269%	37,155
Admixed American	0.0017%	58,890
European (non-Finnish)	0.000595%	167,955

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.Arg910Cys
Coding: c.2728C>T
MANE Select: NM_014633
dbSNP: rs761302085
Type: single nucleotide variant
Location: chr11:10774012 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 910: the 'disordered' region

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

Similar variants

CTR9 p.Arg910His Uncertain significance ★ ⚠ same residue
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

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-arg910cys (accessed [today's date]).

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