DHDDS p.Arg258Gly
c.772C>G · VCV4963378
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2036 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2036 | likely benign |
|---|---|---|
| REVEL | 0.315 | indeterminate |
| SaProt | LLR -10.33 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -1.8, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic |
| Overall | ||
| CADD | 21.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DHDDS
- Protein
- p.Arg258Gly
- Coding
- c.772C>G
- MANE Select
- NM_205861
- Type
- single nucleotide variant
- Location
- chr1:26468901 (GRCh38)
- Gene constraint
- LOEUF 0.536 · pLI 0.91 (gnomAD)
- Structure
- AlphaFold pLDDT 95.01 · 9 PDB
- Residue 258
- a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); an α-helix
Similar variants
- DHDDS p.Arg258Gln Uncertain significance ★★ ⚠ same residue
- DHDDS p.Arg258Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
- DHDDS p.Arg258fs Uncertain significance ★ same residue
- DHDDS c.658-2A>G Likely pathogenic ★★ same type
- DHDDS p.Arg205Gln Pathogenic ★★ same type
- DHDDS p.Arg211Gln Pathogenic ★★ same type
- DHDDS p.Arg37Cys Pathogenic ★★ same type
- DHDDS p.Arg37His Pathogenic/Likely pathogenic ★★ 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/dhdds-p-arg258gly (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown