Is IPO8 p.Pro513fs (c.1538del) pathogenic?

IPO8 p.Pro513fs (c.1538del) is classified Pathogenic in IPO8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-22). No gnomAD frequency available for this variant; Associated with IPO8 related Connective tissue disorder.

What condition is associated with IPO8 p.Pro513fs (c.1538del)?

IPO8 p.Pro513fs (c.1538del) is associated with IPO8 related Connective tissue disorder (ClinVar).

How common is IPO8 p.Pro513fs (c.1538del) in the general population?

IPO8 p.Pro513fs (c.1538del) is no gnomAD frequency available for this variant (gnomAD).

IPO8 p.Pro513fs

c.1538del · rs2136150891 · VCV1064724

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

IPO8 related Connective tissue disorder

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 14 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2	GERP -4.4

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.Pro513fs
Coding: c.1538del
MANE Select: NM_006390
dbSNP: rs2136150891
Type: Deletion
Location: chr12:30663545 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 87.59
Residue 513: 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); a UniProt-annotated variant site (in viss; undetectable protein levels in patient's fibroblasts, although mrna levels seem unaffected)

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

Disease context

IPO8 related Connective tissue disorder

Similar variants

IPO8 p.Leu783fs Pathogenic ★ same condition
IPO8 p.Leu866fs Pathogenic ★ same condition
IPO8 p.Val257fs Pathogenic ★ same condition
IPO8 c.2695+3_2695+7del Pathogenic same condition
IPO8 p.Pro243fs Pathogenic same condition
IPO8 c.2900-1G>A Pathogenic/Likely pathogenic ★★ same condition
IPO8 p.Arg474Ter Pathogenic ★★ same condition
IPO8 p.Trp259Ter 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-pro513fs (accessed [today's date]).

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