DRAM2 p.Ala63=
c.189G>A · rs368808594 · VCV1379686
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.7 | GERP -5.1 |
| Overall | ||
| CADD | 0.831 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,072 alleles
Filtering AF
0.00581%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00277%
Overall
0.00311%
50/1,608,092 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,036 |
| East Asian | 0.0112% | 8,945 |
| African / African-American | 0.00673% | 14,858 |
| Admixed American | 0.00669% | 14,940 |
| South Asian | 0.00661% | 15,120 |
| European (non-Finnish) | 0.0023% | 43,558 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,254 |
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
- DRAM2
- Protein
- p.Ala63=
- Coding
- c.189G>A
- MANE Select
- NM_001349884
- dbSNP
- rs368808594
- Type
- single nucleotide variant
- Location
- chr1:111126237 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.35
Similar variants
- DRAM2 p.Ala63Val Uncertain significance ★ ⚠ same residue
- DRAM2 c.340-2A>G Pathogenic/Likely pathogenic ★★ same type
- DRAM2 c.518-1G>A Likely pathogenic ★★ same type
- DRAM2 c.601-1G>A Likely pathogenic ★★ same type
- DRAM2 p.Gln147Ter Pathogenic/Likely pathogenic ★★ same type
- DRAM2 p.Trp165Ter Pathogenic ★★ same type
- DRAM2 c.199+6T>G Uncertain significance ★★ same type
- DRAM2 p.Ala39Thr 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/dram2-p-ala63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown