Is IMPG2 p.Trp758Ter (c.2274G>A) pathogenic?

IMPG2 p.Trp758Ter (c.2274G>A) is classified Pathogenic/Likely pathogenic in IMPG2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-01). Absent from gnomAD v4.1; Associated with IMPG2-related disorders.

What condition is associated with IMPG2 p.Trp758Ter (c.2274G>A)?

IMPG2 p.Trp758Ter (c.2274G>A) is associated with IMPG2-related disorders, vitelliform macular dystrophy 5, retinitis pigmentosa (ClinVar).

How common is IMPG2 p.Trp758Ter (c.2274G>A) in the general population?

IMPG2 p.Trp758Ter (c.2274G>A) is absent from gnomAD v4.1 (gnomAD).

IMPG2 p.Trp758Ter

c.2274G>A · rs786205564 · VCV191180

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

IMPG2-related disorders

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 1	GERP 1.7
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IMPG2
Protein: p.Trp758Ter
Coding: c.2274G>A
MANE Select: NM_016247
dbSNP: rs786205564
Type: single nucleotide variant
Location: chr3:101244057 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 758: 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

IMPG2-related disorders

Also linked: vitelliform macular dystrophy 5 retinitis pigmentosa

Similar variants

IMPG2 c.1240-1G>A Likely pathogenic ★★ same condition
IMPG2 c.1240-2A>G Pathogenic/Likely pathogenic ★★ same condition
IMPG2 c.502-2A>G Likely pathogenic ★★ same condition
IMPG2 c.667-1G>A Pathogenic/Likely pathogenic ★★ same condition
IMPG2 c.829-1G>T Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg127Ter Pathogenic ★★ same condition
IMPG2 p.Arg906Ter 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-trp758ter (accessed [today's date]).

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