DHDDS p.Gln140=
c.420G>A · VCV4809835
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
retinitis pigmentosa 59
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.088 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.3 | GERP -0.61, phastCons 1 |
| Overall | ||
| CADD | 8.463 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/75,004 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000205%
3/1,461,582 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,502 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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.Gln140=
- Coding
- c.420G>A
- MANE Select
- NM_205861
- Type
- single nucleotide variant
- Location
- chr1:26446412 (GRCh38)
- Gene constraint
- LOEUF 0.536 · pLI 0.91 (gnomAD)
- Structure
- AlphaFold pLDDT 95.01 · 9 PDB
- Residue 140
- a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); an α-helix
Similar variants
- DHDDS p.Gln140Arg Uncertain significance ★★ ⚠ 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
- DHDDS p.Gly35Glu Pathogenic/Likely 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-gln140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown