DHDDS p.Gln48His
c.144G>C · rs1057088171 · VCV2051201
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3803 | ambiguous |
|---|---|---|
| REVEL | 0.139 | moderately benign-leaning |
| SaProt | LLR -6.92 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -4, phastCons 1 |
| Regional constraint | o/e 0.58 | unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic |
| Overall | ||
| CADD | 16.31 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,249 |
| East Asiangrpmax | 0.00223% | 44,880 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- DHDDS
- Protein
- p.Gln48His
- Coding
- c.144G>C
- MANE Select
- NM_205861
- dbSNP
- rs1057088171
- Type
- single nucleotide variant
- Location
- chr1:26438248 (GRCh38)
- Gene constraint
- LOEUF 0.536 · pLI 0.91 (gnomAD)
- Structure
- AlphaFold pLDDT 95.01 · 9 PDB
- Residue 48
- an α-helix
Similar variants
- DHDDS p.Gln48Arg Uncertain significance ★ ⚠ same residue
- DHDDS p.Gln48= Likely benign ★ same residue
- DHDDS c.658-2A>G Likely pathogenic ★★ same condition
- DHDDS p.Arg205Gln Pathogenic ★★ same condition
- DHDDS p.Arg211Gln Pathogenic ★★ same condition
- DHDDS p.Arg37Cys Pathogenic ★★ same condition
- DHDDS p.Arg37His Pathogenic/Likely pathogenic ★★ same condition
- DHDDS p.Arg37Ser Pathogenic ★★ same condition
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/dhdds-p-gln48his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown