Is IMPG1 p.Pro430fs (c.1287_1288insG) pathogenic?

IMPG1 p.Pro430fs (c.12871288insG) is classified Uncertain significance in IMPG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). Associated with retinitis pigmentosa.

What condition is associated with IMPG1 p.Pro430fs (c.1287_1288insG)?

IMPG1 p.Pro430fs (c.1287_1288insG) is associated with retinitis pigmentosa, cone-rod dystrophy (ClinVar).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

IMPG1 p.Pro430fs

c.1287_1288insG · VCV3544465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

retinitis pigmentosa

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 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.15, phastCons 1

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

Variant & gene context

Gene: IMPG1
Protein: p.Pro430fs
Coding: c.1287_1288insG
MANE Select: NM_001563
Type: Insertion
Location: chr6:76002921 (GRCh38)
Gene constraint: LOEUF 1.217 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.26

Full IMPG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone-rod dystrophy

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

IMPG1 c.1291+1G>T Pathogenic/Likely pathogenic ★★ same condition
IMPG1 c.1824+1G>A Pathogenic/Likely pathogenic ★★ same condition
IMPG1 p.Ser360Thr Uncertain significance ★★ ⚠ same condition
IMPG1 c.1135+5G>A Uncertain significance ★ same condition
IMPG1 p.Leu626Phe Conflicting classifications of pathogenicity ★ ⚠ same condition
IMPG1 p.Lys248Gln Uncertain significance ★ ⚠ same condition
IMPG1 p.Arg6fs Pathogenic ★ same type
IMPG1 p.Asp505fs Pathogenic ★ 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/impg1-p-pro430fs (accessed [today's date]).

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