Is CTR9 p.Arg864His (c.2591G>A) pathogenic?

CTR9 p.Arg864His (c.2591G>A) is classified Likely benign in CTR9 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-20). AlphaMissense: likely benign (0.0833); Very rare (popmax 0.00808%, nfe).

How common is CTR9 p.Arg864His (c.2591G>A) in the general population?

CTR9 p.Arg864His (c.2591G>A) is very rare (popmax 0.00808%, nfe) (gnomAD).

What do computational predictors say about CTR9 p.Arg864His (c.2591G>A)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

CTR9 p.Arg864His

c.2591G>A · rs542399971 · VCV1160422

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00808%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -9.93	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	27.6	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 0.00808% European (non-Finnish) · 95/1,176,328 alleles

Filtering AF 0.00675% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00626%

Overall 0.00945% 151/1,597,528 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0814%	1,229
European (non-Finnish)grpmax	0.00808%	12,382
Remaining individualsnot grpmax-eligible	0.00485%	20,621
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,088

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg864His
Coding: c.2591G>A
MANE Select: NM_014633
dbSNP: rs542399971
Type: single nucleotide variant
Location: chr11:10773137 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 864: an α-helix

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

Similar variants

CTR9 p.Arg864Cys Uncertain significance ★ ⚠ same residue
CTR9 p.Arg864= Likely benign ★ 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

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-arg864his (accessed [today's date]).

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