Is IMPG2 p.Leu367fs (c.1100dup) pathogenic?

IMPG2 p.Leu367fs (c.1100dup) is classified Pathogenic/Likely pathogenic in IMPG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-26). Very rare (popmax 0.00223%, eas); Associated with IMPG2-related disorders.

What condition is associated with IMPG2 p.Leu367fs (c.1100dup)?

IMPG2 p.Leu367fs (c.1100dup) is associated with IMPG2-related disorders (ClinVar).

How common is IMPG2 p.Leu367fs (c.1100dup) in the general population?

IMPG2 p.Leu367fs (c.1100dup) is very rare (popmax 0.00223%, eas) (gnomAD).

IMPG2 p.Leu367fs

c.1100dup · rs1260931426 · VCV1440615

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 10 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 0.84, phastCons 1
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

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,204 alleles · very rare exomes 5/1,461,154 · genomes 1/152,050 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
European (non-Finnish)	0.000424%	235,903

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.Leu367fs
Coding: c.1100dup
MANE Select: NM_016247
dbSNP: rs1260931426
Type: Duplication
Location: chr3:101257581 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 367: 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

Similar variants

IMPG2 c.3023-6_3030dup Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Asp23fs Pathogenic ★★ same condition
IMPG2 p.Cys1077fs Pathogenic ★★ same condition
IMPG2 p.Gln607fs Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Asn956fs Pathogenic ★ same condition
IMPG2 p.Gly286fs Likely pathogenic ★ same condition
IMPG2 p.Ser482Ter Likely pathogenic ★ same condition
IMPG2 p.Leu367= Likely benign ★ same residue

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-leu367fs (accessed [today's date]).

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