Is IMPG2 p.Gln1237del (c.3706CAA[1]) pathogenic?

IMPG2 p.Gln1237del (c.3706CAA[1]) is classified Uncertain significance in IMPG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-01). Very rare (popmax 0.0056%, nfe).

How common is IMPG2 p.Gln1237del (c.3706CAA[1]) in the general population?

IMPG2 p.Gln1237del (c.3706CAA[1]) is very rare (popmax 0.0056%, nfe) (gnomAD).

IMPG2 p.Gln1237del

c.3706CAA[1] · rs759574080 · VCV1002947

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0056%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP -1, phastCons 1
Overall
CADD	12.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0056% European (non-Finnish) · 66/1,179,388 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00412%

Overall 0.00471% 76/1,613,284 alleles · very rare exomes 73/1,461,134 · genomes 3/152,150 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0112%	8,923
European (non-Finnish)grpmax	0.0056%	17,870
South Asian	0.0022%	45,534
African / African-American	0.00134%	74,890

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln1237del
Coding: c.3706CAA[1]
MANE Select: NM_016247
dbSNP: rs759574080
Type: Microsatellite
Location: chr3:101228799 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 1237: 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

Similar variants

IMPG2 p.Leu1053_Cys1054insTer Pathogenic ★★ same type
IMPG2 p.Ser527fs Pathogenic ★★ same type
IMPG2 p.Pro434del Uncertain significance ★★ same type
IMPG2 p.Arg782fs Likely pathogenic ★ same type
IMPG2 p.Glu1033fs Pathogenic ★ same type
IMPG2 c.3423-7_3423-4del Conflicting classifications of pathogenicity ★ same type
IMPG2 p.Asn415del Uncertain significance ★ same type
IMPG2 p.Glu272del Uncertain significance ★ same type

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-gln1237del (accessed [today's date]).

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