Is IPO11 p.Val77Ile (c.229G>A) pathogenic?

IPO11 p.Val77Ile (c.229G>A) is classified Uncertain significance in IPO11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0885); No allele count reported in gnomAD v4.1 (AN 1,603,294).

How common is IPO11 p.Val77Ile (c.229G>A) in the general population?

IPO11 p.Val77Ile (c.229G>A) is no allele count reported in gnomAD v4.1 (AN 1,603,294) (gnomAD).

What do computational predictors say about IPO11 p.Val77Ile (c.229G>A)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

IPO11 p.Val77Ile

c.229G>A · VCV4276144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,294)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.95	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 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 48 kb · p 0.2 · regional, not allelic
Overall
CADD	23.8	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

No allele count reported in gnomAD v4.1 (AN 1,603,294). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: IPO11
Protein: p.Val77Ile
Coding: c.229G>A
MANE Select: NM_016338
Type: single nucleotide variant
Location: chr5:62443073 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 93.53
Residue 77: the importin n-terminal domain

Full IPO11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IPO11 p.Thr409Ala Uncertain significance ★★ ⚠ same type
IPO11 p.Ala726= Benign ★★ same type
IPO11 p.Asn260Asp Benign ★★ same type
IPO11 p.Leu112= Benign ★★ same type
IPO11 p.Leu246= Benign ★★ same type
IPO11 p.Leu799= Benign ★★ same type
IPO11 p.Ala110Val Uncertain significance ★ ⚠ same type
IPO11 p.Ala332Thr 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/ipo11-p-val77ile (accessed [today's date]).

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