DTHD1 p.Ser430=
c.1290G>A · rs752685129 · VCV1120993
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0286%, sas)
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 -2.3 | GERP -4.2 |
| Overall | ||
| CADD | 1.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0286%
South Asian · 24/83,812 alleles
Filtering AF
0.0197%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0167%
Overall
0.00749%
116/1,549,580 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0286% | 3,492 |
| Finnishnot grpmax-eligible | 0.01% | 9,972 |
| Remaining individualsnot grpmax-eligible | 0.00834% | 11,995 |
| European (non-Finnish) | 0.00672% | 14,880 |
| African / African-American | 0.00274% | 36,509 |
| East Asian | 0.00245% | 40,840 |
| Admixed American | 0.00196% | 50,894 |
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
- DTHD1
- Protein
- p.Ser430=
- Coding
- c.1290G>A
- MANE Select
- NM_001170700
- dbSNP
- rs752685129
- Type
- single nucleotide variant
- Location
- chr4:36293597 (GRCh38)
- Gene constraint
- LOEUF 1.034 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.99
- Residue 430
- the zu5 2 domain
Similar variants
- DTHD1 c.1218+1G>A Uncertain significance ★★ same type
- DTHD1 c.1219-2A>G Uncertain significance ★★ same type
- DTHD1 p.Ala552Ser Uncertain significance ★★ ⚠ same type
- DTHD1 p.Ala811Asp Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg326Gln Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg371Cys Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg447Gln Uncertain significance ★★ ⚠ same type
- DTHD1 p.Arg447Ter 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/dthd1-p-ser430 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown