IMPG2 p.Asp598=
c.1794C>T · rs371805004 · VCV287577
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP -4.3, phastCons 0.99 |
| Overall | ||
| CADD | 4.811 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
European (non-Finnish) · 196/1,171,514 alleles
Filtering AF
0.0148%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0141%
Overall
0.0135%
216/1,597,188 alleles · ultra-rare
exomes 208/1,445,082 · genomes 8/152,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0167% | 5,977 |
| Remaining individualsnot grpmax-eligible | 0.00974% | 10,268 |
| African / African-American | 0.00811% | 12,337 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00693% | 14,438 |
| Admixed American | 0.00348% | 28,767 |
| South Asian | 0.00339% | 29,510 |
| Finnishnot grpmax-eligible | 0.00157% | 63,562 |
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.Asp598=
- Coding
- c.1794C>T
- MANE Select
- NM_016247
- dbSNP
- rs371805004
- Type
- single nucleotide variant
- Location
- chr3:101244537 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
- Residue 598
- a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5)
Similar variants
- IMPG2 c.1240-1G>A Likely pathogenic ★★ same type
- IMPG2 c.1240-2A>G Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.502-2A>G Likely pathogenic ★★ same type
- IMPG2 c.583+1G>C Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.667-1G>A Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.828+1G>A Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.829-1G>T Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.829-2A>T Pathogenic/Likely pathogenic ★★ 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-asp598 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown