IMPG2 p.Leu983=
c.2949G>A · rs767140573 · VCV1465624
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 0.41 | GERP -2.2, phastCons 0.99 |
| Overall | ||
| CADD | 6.929 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.000991%
16/1,613,942 alleles · ultra-rare
exomes 16/1,461,752 · genomes 0/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| South Asian | 0.0132% | 7,589 |
| Admixed American | 0.00167% | 59,990 |
| European (non-Finnish) | 8.48e-05% | 1,179,920 |
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.Leu983=
- Coding
- c.2949G>A
- MANE Select
- NM_016247
- dbSNP
- rs767140573
- Type
- single nucleotide variant
- Location
- chr3:101242761 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
- Residue 983
- a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the sea 2 domain
Similar variants
- IMPG2 p.Leu983Pro Uncertain significance ★ ⚠ same residue
- 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
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-leu983 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown