Is IMPG2 p.Ser527fs (c.1578_1581del) pathogenic?

IMPG2 p.Ser527fs (c.15781581del) is classified Pathogenic in IMPG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-10). Very rare (popmax 8.48e-05%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with IMPG2 p.Ser527fs (c.1578_1581del)?

IMPG2 p.Ser527fs (c.1578_1581del) is associated with inherited retinal dystrophy (ClinVar).

How common is IMPG2 p.Ser527fs (c.1578_1581del) in the general population?

IMPG2 p.Ser527fs (c.1578_1581del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

IMPG2 p.Ser527fs

c.1578_1581del · rs1559643320 · VCV631902

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

inherited retinal dystrophy

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 13 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.2	GERP -4.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,938 alleles

Overall 6.2e-05% 1/1,614,060 alleles · very rare exomes 1/1,461,734 · genomes 0/152,326 · 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.Ser527fs
Coding: c.1578_1581del
MANE Select: NM_016247
dbSNP: rs1559643320
Type: Microsatellite
Location: chr3:101244750 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 527: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5)

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IMPG2 c.3423-7_3423-4del Conflicting classifications of pathogenicity ★ same condition
IMPG2 p.Asn415del Uncertain significance ★ same condition
IMPG2 p.Ser527Ala Uncertain significance ★ ⚠ same residue
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg906Ter Pathogenic ★★ same condition
IMPG2 p.Arg964Ter Pathogenic ★★ same condition
IMPG2 p.Asp23fs Pathogenic ★★ same condition
IMPG2 p.Gln363Ter 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-ser527fs (accessed [today's date]).

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