Is IMPG2 p.Ser482Ter (c.1443dup) pathogenic?

IMPG2 p.Ser482Ter (c.1443dup) is classified Likely pathogenic in IMPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-29). Very rare (popmax 0.000169%, nfe); Associated with IMPG2-related disorders.

What condition is associated with IMPG2 p.Ser482Ter (c.1443dup)?

IMPG2 p.Ser482Ter (c.1443dup) is associated with IMPG2-related disorders (ClinVar).

How common is IMPG2 p.Ser482Ter (c.1443dup) in the general population?

IMPG2 p.Ser482Ter (c.1443dup) is very rare (popmax 0.000169%, nfe) (gnomAD).

IMPG2 p.Ser482Ter

c.1443dup · VCV4963534

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,034 alleles

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

Overall 0.000124% 2/1,614,216 alleles · very rare exomes 2/1,461,862 · genomes 0/152,354 · 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.Ser482Ter
Coding: c.1443dup
MANE Select: NM_016247
Type: Duplication
Location: chr3:101245901 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 482: 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.Leu367fs Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Ser482= Likely benign ★★ same residue
IMPG2 p.Asn956fs Pathogenic ★ same condition
IMPG2 p.Gly286fs 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-ser482ter (accessed [today's date]).

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