Is IMPG2 p.Ser522Ter (c.1565C>G) pathogenic?

IMPG2 p.Ser522Ter (c.1565C>G) is classified Pathogenic/Likely pathogenic in IMPG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-07-07). Very rare (popmax 0.00017%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with IMPG2 p.Ser522Ter (c.1565C>G)?

IMPG2 p.Ser522Ter (c.1565C>G) is associated with inherited retinal dystrophy (ClinVar).

How common is IMPG2 p.Ser522Ter (c.1565C>G) in the general population?

IMPG2 p.Ser522Ter (c.1565C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

IMPG2 p.Ser522Ter

c.1565C>G · rs1409688898 · VCV450088

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -0.99, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,826 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,818 alleles · very rare exomes 2/1,461,494 · genomes 0/152,324 · 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.Ser522Ter
Coding: c.1565C>G
MANE Select: NM_016247
dbSNP: rs1409688898
Type: single nucleotide variant
Location: chr3:101244766 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 522: 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 p.Ser522= Likely benign ★ same residue
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg906Ter Pathogenic ★★ same condition
IMPG2 p.Arg964Ter Pathogenic ★★ same condition
IMPG2 p.Gln363Ter Pathogenic ★★ same condition
IMPG2 p.Gln814Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Gln856Ter Pathogenic ★★ same condition
IMPG2 p.Glu1164Ter Pathogenic/Likely 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-ser522ter (accessed [today's date]).

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