Computational evidence
| Protein change | ||
| AlphaMissense | 0.0447 | likely benign |
|---|---|---|
| REVEL | 0.106 | moderately benign-leaning |
| SaProt | LLR 0.83 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP 0.54, phastCons 1 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic |
| Overall | ||
| CADD | 17.24 | 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 |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| Finnishnot grpmax-eligible | 100% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 100% | 1 |
| Amishnot grpmax-eligible | 100% | 1 |
| European (non-Finnish) | 100% | 1 |
| Admixed American | 100% | 1 |
| Remaining individualsnot grpmax-eligible | 100% | 1 |
| South Asian | 100% | 1 |
| Middle Eastern | 100% | 1 |
| African / African-American | 99.3% | 1 |
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
- DRC1
- Protein
- p.Trp399Arg
- Coding
- c.1195T>C
- MANE Select
- NM_145038
- dbSNP
- rs939820
- Type
- single nucleotide variant
- Location
- chr2:26444747 (GRCh38)
- Gene constraint
- LOEUF 0.867 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.44 · 1 PDB
- Residue 399
- a UniProt-annotated variant site (in spgf80); a UniProt-annotated variant site (in cild21); a UniProt-annotated variant site (in)
Disease context
primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: primary ciliary dyskinesia 21
For Primary ciliary dyskinesia (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, X-linked recessive
- Onset
- Neonatal
- Prevalence
- 1-5 / 10 000 (Pakistan)
Similar variants
- DRC1 p.Trp399Ter Likely pathogenic ★ same residue
- DRC1 p.Trp399Gln Uncertain significance ★ same residue
- DRC1 p.Gln118Ter Pathogenic/Likely pathogenic ★★ same condition
- DRC1 p.Gln337Ter Pathogenic/Likely pathogenic ★★ same condition
- DRC1 p.Ser642Ter Pathogenic/Likely pathogenic ★★ same condition
- DRC1 p.Ala250Val Uncertain significance ★★ ⚠ same condition
- DRC1 p.Ala391Val Uncertain significance ★★ ⚠ same condition
- DRC1 p.Ala416Gly Uncertain significance ★★ ⚠ 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/drc1-p-trp399arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown