Is IPO8 p.Val334fs (c.1000dup) pathogenic?

IPO8 p.Val334fs (c.1000dup) is classified Pathogenic in IPO8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-18). No gnomAD frequency available for this variant; Associated with IPO8-related aortopathy.

What condition is associated with IPO8 p.Val334fs (c.1000dup)?

IPO8 p.Val334fs (c.1000dup) is associated with IPO8-related aortopathy (ClinVar).

How common is IPO8 p.Val334fs (c.1000dup) in the general population?

IPO8 p.Val334fs (c.1000dup) is no gnomAD frequency available for this variant (gnomAD).

IPO8 p.Val334fs

c.1000dup · rs2136158926 · VCV1047910

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

IPO8-related aortopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: IPO8
Protein: p.Val334fs
Coding: c.1000dup
MANE Select: NM_006390
dbSNP: rs2136158926
Type: Duplication
Location: chr12:30671005 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 87.59
Residue 334: a UniProt-annotated variant site (in viss; undetectable protein levels in either patient's fibroblasts or patient's epstein-barr virus-immortalized b cell lines); a UniProt-annotated variant site (in viss)

Full IPO8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

IPO8-related aortopathy

Similar variants

IPO8 c.2900-1G>A Pathogenic/Likely pathogenic ★★ same condition
IPO8 p.Arg474Ter Pathogenic ★★ same condition
IPO8 p.Trp259Ter Pathogenic ★★ same condition
IPO8 c.1428+5G>A Pathogenic ★ same condition
IPO8 p.Arg971Ter Likely pathogenic ★ same condition
IPO8 p.Leu783fs Pathogenic ★ same condition
IPO8 p.Leu866fs Pathogenic ★ same condition
IPO8 p.Trp229Ter Pathogenic ★ same condition

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/ipo8-p-val334fs (accessed [today's date]).

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