DACH1 p.Val375=
c.1125C>G · rs144078930 · VCV774219
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.25%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -5.9 |
| Overall | ||
| CADD | 0.095 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.25%
Admixed American · 1,664/51,204 alleles
Filtering AF
3.12%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.07%
Overall
0.115%
1,820/1,582,204 alleles · low-frequency
exomes 1,438/1,430,002 · genomes 382/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 3.25% | 31 |
| Remaining individualsnot grpmax-eligible | 0.103% | 970 |
| South Asian | 0.0457% | 2,186 |
| African / African-American | 0.0396% | 2,524 |
| Middle Eastern | 0.0342% | 2,922 |
| East Asian | 0.0204% | 4,900 |
| European (non-Finnish) | 0.0012% | 83,506 |
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
- DACH1
- Protein
- p.Val375=
- Coding
- c.1125C>G
- MANE Select
- NM_080759
- dbSNP
- rs144078930
- Type
- single nucleotide variant
- Location
- chr13:71630557 (GRCh38)
- Gene constraint
- LOEUF 0.371 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 58.74 · 1 PDB
- Residue 375
- the 'interaction with six6 and hdac3' region; the 'disordered' region
Similar variants
- DACH1 c.1722+6C>T Conflicting classifications of pathogenicity ★ same type
- DACH1 p.Ala109Val Uncertain significance ★ ⚠ same type
- DACH1 p.Ala36Glu Uncertain significance ★ ⚠ same type
- DACH1 p.Ala36Val Uncertain significance ★ ⚠ same type
- DACH1 p.Ala418Thr Uncertain significance ★ ⚠ same type
- DACH1 p.Ala533Thr Uncertain significance ★ ⚠ same type
- DACH1 p.Ala586Thr Uncertain significance ★ ⚠ same type
- DACH1 p.Ala64Val 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/dach1-p-val375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown