AMPD2 c.2157+66G>C
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.73%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +66 | deep intronic (+66 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP 0.16 |
| Overall | ||
| CADD | 2.971 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.73%
African / African-American · 3,187/67,386 alleles
Filtering AF
4.59%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.54%
Overall
0.294%
3,827/1,302,908 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.73% | 21 |
| Admixed American | 0.407% | 246 |
| Middle Eastern | 0.384% | 260 |
| Remaining individualsnot grpmax-eligible | 0.38% | 263 |
| European (non-Finnish) | 0.0223% | 4,488 |
| South Asian | 0.014% | 7,151 |
| East Asian | 0.00504% | 19,853 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00373% | 26,844 |
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
- Coding
- c.2157+66G>C
- MANE Select
- NM_001368809
- dbSNP
- rs181839364
- Type
- single nucleotide variant
- Location
- chr1:109630472 (GRCh38)
- Gene constraint
- LOEUF 0.705 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.28 · 5 PDB
Similar variants
- AMPD2 c.1698+1G>A Pathogenic/Likely pathogenic ★★ same type
- AMPD2 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same type
- AMPD2 p.Arg449Ter Pathogenic/Likely pathogenic ★★ same type
- AMPD2 p.Arg620His Pathogenic/Likely pathogenic ★★ same type
- AMPD2 p.Arg789His Likely pathogenic ★★ same type
- AMPD2 p.Glu174Ter Pathogenic/Likely pathogenic ★★ same type
- AMPD2 c.1080+3G>A Uncertain significance ★★ same type
- AMPD2 c.353+3G>A Uncertain significance ★★ 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/ampd2-c-2157-plus-66g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown