Is IPO9 p.Arg882Cys (c.2644C>T) pathogenic?

IPO9 p.Arg882Cys (c.2644C>T) is classified Uncertain significance in IPO9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0995); Ultra-rare (popmax 0.0172%, nfe).

How common is IPO9 p.Arg882Cys (c.2644C>T) in the general population?

IPO9 p.Arg882Cys (c.2644C>T) is ultra-rare (popmax 0.0172%, nfe) (gnomAD).

What do computational predictors say about IPO9 p.Arg882Cys (c.2644C>T)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

IPO9 p.Arg882Cys

c.2644C>T · rs369658460 · VCV3110357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 4,766 bp · p 0.00019 · regional, not allelic
Overall
CADD	26.5	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 0.0172% European (non-Finnish) · 203/1,179,960 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0145%

Overall 0.0133% 214/1,613,782 alleles · ultra-rare exomes 200/1,461,716 · genomes 14/152,066 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0172%	5,813
Middle Eastern	0.0165%	6,074
Remaining individualsnot grpmax-eligible	0.0144%	6,941
African / African-American	0.00134%	74,848

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: IPO9
Protein: p.Arg882Cys
Coding: c.2644C>T
MANE Select: NM_018085
dbSNP: rs369658460
Type: single nucleotide variant
Location: chr1:201872895 (GRCh38)
Gene constraint: LOEUF 0.31 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.37 · 7 PDB
Residue 882: a β-strand

Full IPO9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IPO9 p.Gln558= Benign ★★ same type
IPO9 p.Ala10Val Uncertain significance ★ ⚠ same type
IPO9 p.Ala131Val Uncertain significance ★ ⚠ same type
IPO9 p.Ala166Pro Uncertain significance ★ ⚠ same type
IPO9 p.Ala342Gly Uncertain significance ★ ⚠ same type
IPO9 p.Ala418Gly Uncertain significance ★ ⚠ same type
IPO9 p.Ala425Thr Uncertain significance ★ ⚠ same type
IPO9 p.Ala498Ser 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/ipo9-p-arg882cys (accessed [today's date]).

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