AMPD2 p.Pro179=
c.537G>A · rs776483432 · VCV541842
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Conditions
2
pontocerebellar hypoplasia type 9
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.028 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -5 | GERP -3.2 |
| Overall | ||
| CADD | 1.172 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,068 alleles
Filtering AF
0.00581%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.00174%
28/1,612,536 alleles · ultra-rare
exomes 19/1,460,424 · genomes 9/152,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,034 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,797 |
| East Asian | 0.00446% | 22,436 |
| African / African-American | 0.00267% | 37,441 |
| South Asian | 0.0022% | 45,505 |
| Admixed American | 0.00167% | 59,816 |
| European (non-Finnish) | 0.00136% | 73,697 |
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
- AMPD2
- Protein
- p.Pro179=
- Coding
- c.537G>A
- MANE Select
- NM_001368809
- dbSNP
- rs776483432
- Type
- single nucleotide variant
- Location
- chr1:109626731 (GRCh38)
- Gene constraint
- LOEUF 0.705 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.28 · 5 PDB
Similar variants
- AMPD2 p.Pro179Leu Uncertain significance ★ ⚠ same residue
- AMPD2 c.1698+1G>A Pathogenic/Likely pathogenic ★★ same condition
- AMPD2 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same condition
- AMPD2 p.Arg449Ter Pathogenic/Likely pathogenic ★★ same condition
- AMPD2 p.Arg620His Pathogenic/Likely pathogenic ★★ same condition
- AMPD2 p.Arg789His Likely pathogenic ★★ same condition
- AMPD2 p.Glu174Ter Pathogenic/Likely pathogenic ★★ same condition
- AMPD2 c.1080+3G>A 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/ampd2-p-pro179 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown