DMAC1 p.Ala20Thr
c.58G>A · VCV3840426
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0388%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.019 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.9 | GERP -3.4 |
| Regional constraint | o/e 1.38 | unconstrained · MANE · 1,158 bp · p 1.7e-06 · regional, not allelic |
| Overall | ||
| CADD | 3.052 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0388%
African / African-American · 29/74,824 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0239%
Overall
0.00237%
38/1,603,268 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0388% | 2,580 |
| Admixed American | 0.0101% | 9,950 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,056 |
| European (non-Finnish) | 8.5e-05% | 1,176,914 |
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
- DMAC1
- Protein
- p.Ala20Thr
- Coding
- c.58G>A
- MANE Select
- NM_033428
- Type
- single nucleotide variant
- Location
- chr9:7799677 (GRCh38)
- Gene constraint
- LOEUF 1.842 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.00
- Residue 20
- the 'disordered' region
Similar variants
- DMAC1 p.Ala21Gly Uncertain significance ★ same type
- DMAC1 p.Ala24Gly Uncertain significance ★ same type
- DMAC1 p.Ala30Ser Uncertain significance ★ same type
- DMAC1 p.Ala39Gly Uncertain significance ★ same type
- DMAC1 p.Arg110Cys Uncertain significance ★ same type
- DMAC1 p.Arg110His Uncertain significance ★ same type
- DMAC1 p.Arg42His Uncertain significance ★ same type
- DMAC1 p.Gln86Arg 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/dmac1-p-ala20thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown