DRAM2 p.Pro197=
c.591C>T · VCV4692676
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 -0.58 | |
| Overall | ||
| CADD | 6.896 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00136%
22/1,612,342 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| African / African-American | 0.00267% | 37,456 |
| East Asian | 0.00223% | 44,836 |
| Admixed American | 0.00167% | 59,894 |
| European (non-Finnish) | 0.00136% | 73,676 |
| South Asian | 0.0011% | 91,002 |
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.Pro197=
- Coding
- c.591C>T
- MANE Select
- NM_001349884
- Type
- single nucleotide variant
- Location
- chr1:111119886 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.35
Similar variants
- 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
- DRAM2 p.Ala69Val 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-pro197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown