IMPG2 p.His104=
c.312T>C · rs780780062 · VCV1987528
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.74 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.089 | GERP -0.91 |
| Overall | ||
| CADD | 6.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,890 alleles
Filtering AF
0.00901%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00682%
Overall
0.000682%
11/1,613,546 alleles · ultra-rare
exomes 9/1,461,374 · genomes 2/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 5,989 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,468 |
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.His104=
- Coding
- c.312T>C
- MANE Select
- NM_016247
- dbSNP
- rs780780062
- Type
- single nucleotide variant
- Location
- chr3:101319606 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
Similar variants
- IMPG2 p.His104Arg Uncertain significance ★ ⚠ same residue
- IMPG2 p.His104Tyr Uncertain significance ★ ⚠ same residue
- IMPG2 p.His104fs Likely pathogenic ★ 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
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-his104 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown