Is IMPG2 p.Asp23fs (c.68dup) pathogenic?

IMPG2 p.Asp23fs (c.68dup) is classified Pathogenic in IMPG2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-19). Very rare (popmax 8.68e-05%, nfe); Associated with IMPG2-related disorders.

What condition is associated with IMPG2 p.Asp23fs (c.68dup)?

IMPG2 p.Asp23fs (c.68dup) is associated with IMPG2-related disorders, inherited retinal dystrophy (ClinVar).

How common is IMPG2 p.Asp23fs (c.68dup) in the general population?

IMPG2 p.Asp23fs (c.68dup) is very rare (popmax 8.68e-05%, nfe) (gnomAD).

IMPG2 p.Asp23fs

c.68dup · rs768660614 · VCV236460

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.68e-05%, nfe)

Conditions

IMPG2-related disorders

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 1 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 1.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.68e-05% European (non-Finnish) · 1/1,152,608 alleles

Overall 6.32e-05% 1/1,583,026 alleles · very rare exomes 1/1,430,878 · genomes 0/152,148 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IMPG2
Protein: p.Asp23fs
Coding: c.68dup
MANE Select: NM_016247
dbSNP: rs768660614
Type: Duplication
Location: chr3:101320304 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28

Full IMPG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

IMPG2-related disorders

Also linked: inherited retinal dystrophy

Similar variants

IMPG2 c.3023-6_3030dup Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Cys1077fs Pathogenic ★★ same condition
IMPG2 p.Gln607fs Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Leu367fs Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg68fs Pathogenic ★ same condition
IMPG2 p.Asn956fs Pathogenic ★ same condition
IMPG2 p.Gly286fs Likely pathogenic ★ same condition
IMPG2 p.Leu449fs 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/impg2-p-asp23fs (accessed [today's date]).

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