IMPG2 p.Leu649Pro
c.1946T>C · rs146644083 · VCV167193
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0942 | likely benign |
|---|---|---|
| REVEL | 0.049 | moderately benign-leaning |
| SaProt | LLR -5.65 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.8 | GERP 1.4, phastCons 0.98 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic |
| Overall | ||
| CADD | 17.63 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0507% | 1,972 |
| Admixed American | 0.0117% | 8,570 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 8.47e-05% | 1,180,018 |
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.Leu649Pro
- Coding
- c.1946T>C
- MANE Select
- NM_016247
- dbSNP
- rs146644083
- Type
- single nucleotide variant
- Location
- chr3:101244385 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
- Residue 649
- a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5)
Similar variants
- IMPG2 p.Leu649Val Uncertain significance ★ ⚠ same residue
- IMPG2 p.Ala1230Ser Uncertain significance ★★ ⚠ same condition
- IMPG2 p.Ala1231Val Uncertain significance ★★ ⚠ same condition
- IMPG2 p.Ala207Thr Uncertain significance ★★ ⚠ same condition
- IMPG2 p.Ala280Ser Uncertain significance ★★ ⚠ same condition
- IMPG2 p.Ala419Asp Uncertain significance ★★ ⚠ same condition
- IMPG2 p.Ala741Asp Uncertain significance ★★ ⚠ same condition
- IMPG2 p.Ala978Thr Uncertain significance ★★ ⚠ 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-leu649pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown