IMPG2 p.Pro434del
c.1298CAC[1] · rs776953424 · VCV961278
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00686%, 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 3.6 | GERP 0.31, phastCons 1 |
| Overall | ||
| CADD | 12.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00686%
European (non-Finnish) · 81/1,180,008 alleles
Filtering AF
0.00563%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00527%
85/1,614,034 alleles · very rare
exomes 79/1,461,830 · genomes 6/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00686% | 14,568 |
| Admixed American | 0.00667% | 14,997 |
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.Pro434del
- Coding
- c.1298CAC[1]
- MANE Select
- NM_016247
- dbSNP
- rs776953424
- Type
- Microsatellite
- Location
- chr3:101246042 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
- Residue 434
- a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5)
Similar variants
- IMPG2 p.Pro434Ser Uncertain significance ★★ ⚠ same residue
- IMPG2 p.Leu1053_Cys1054insTer Pathogenic ★★ same type
- IMPG2 p.Ser527fs Pathogenic ★★ same type
- IMPG2 p.Gln1237del 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
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-pro434del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown