DMAC2 p.Val231=
c.693T>C · VCV4660460
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.045 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -3.1 |
| Overall | ||
| CADD | 0.238 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00109%
16/1,461,868 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| African / African-American | 0.0107% | 9,380 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,837 |
| Finnishnot grpmax-eligible | 0.00312% | 32,015 |
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
- DMAC2
- Protein
- p.Val231=
- Coding
- c.693T>C
- MANE Select
- NM_018035
- Type
- single nucleotide variant
- Location
- chr19:41432312 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.56
Similar variants
- DMAC2 p.Val231Ala Uncertain significance ★ ⚠ same residue
- DMAC2 p.His23Arg Likely benign ★★ same type
- DMAC2 p.Ala193Thr Uncertain significance ★ ⚠ same type
- DMAC2 p.Ala237Thr Uncertain significance ★ ⚠ same type
- DMAC2 p.Ala27Val Uncertain significance ★ ⚠ same type
- DMAC2 p.Ala86Thr Uncertain significance ★ ⚠ same type
- DMAC2 p.Arg107Ser Uncertain significance ★ ⚠ same type
- DMAC2 p.Arg146Gly 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/dmac2-p-val231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown