Is IPO9 p.Pro905Ala (c.2713C>G) pathogenic?

IPO9 p.Pro905Ala (c.2713C>G) is classified Uncertain significance in IPO9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1687); Absent from gnomAD v4.1.

How common is IPO9 p.Pro905Ala (c.2713C>G) in the general population?

IPO9 p.Pro905Ala (c.2713C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IPO9 p.Pro905Ala (c.2713C>G)?

AlphaMissense predicts likely benign (score 0.1687) — an in-silico prediction, not a clinical call.

IPO9 p.Pro905Ala

c.2713C>G · VCV4679273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1687	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 4,766 bp · p 0.00019 · regional, not allelic
Overall
CADD	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IPO9
Protein: p.Pro905Ala
Coding: c.2713C>G
MANE Select: NM_018085
Type: single nucleotide variant
Location: chr1:201874252 (GRCh38)
Gene constraint: LOEUF 0.31 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.37 · 7 PDB

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-pro905ala (accessed [today's date]).

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