IMPG1 p.Pro646=
c.1938G>A · rs201013836 · VCV1124561
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0384%, amr)
Conditions
1
inherited retinal dystrophy
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 -14 | GERP -5.2 |
| Overall | ||
| CADD | 1.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0384%
Admixed American · 23/59,974 alleles
Filtering AF
0.0261%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.0162%
262/1,613,742 alleles · ultra-rare
exomes 246/1,461,540 · genomes 16/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0384% | 2,608 |
| East Asian | 0.0223% | 4,487 |
| European (non-Finnish) | 0.0185% | 5,412 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,500 |
| African / African-American | 0.00533% | 18,752 |
| South Asian | 0.0022% | 45,535 |
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
- IMPG1
- Protein
- p.Pro646=
- Coding
- c.1938G>A
- MANE Select
- NM_001563
- dbSNP
- rs201013836
- Type
- single nucleotide variant
- Location
- chr6:75947420 (GRCh38)
- Gene constraint
- LOEUF 1.217 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.26
- Residue 646
- the sea 2 domain
Similar variants
- IMPG1 p.Pro646Ala Uncertain significance ★★ ⚠ same residue
- IMPG1 p.Pro646Leu Uncertain significance ★ same residue
- IMPG1 c.498-1G>C Likely pathogenic ★★ same condition
- IMPG1 p.Trp126Ter Pathogenic/Likely pathogenic ★★ same condition
- IMPG1 p.Arg580Cys Uncertain significance ★★ same condition
- IMPG1 p.Glu695Lys Uncertain significance ★★ ⚠ same condition
- IMPG1 p.His337Arg Uncertain significance ★★ ⚠ same condition
- IMPG1 p.Leu268Ile 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/impg1-p-pro646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown