CLEC18B p.Arg429Cys
c.1285C>T · VCV3493530
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5617 | ambiguous |
|---|---|---|
| REVEL | 0.402 | indeterminate |
| SaProt | LLR -9.50 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP 0.5, phastCons 1 |
| Regional constraint | o/e 0.01 | constrained · MANE · 4,052 bp · p 4.3e-68 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R438C vs ClinVar R429C) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.193% | 519 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,680 |
| South Asiangrpmax | 0.0121% | 8,269 |
| African / African-American | 0.012% | 8,325 |
| East Asian | 0.00223% | 44,820 |
| Admixed American | 0.00167% | 59,936 |
| Finnishnot grpmax-eligible | 0.00156% | 64,026 |
| European (non-Finnish) | 0.00119% | 84,271 |
Ashkenazi Jewish 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
- CLEC18B
- Protein
- p.Arg429Cys
- Coding
- c.1285C>T
- MANE Select
- NM_001385193
- Type
- single nucleotide variant
- Location
- chr16:74409568 (GRCh38)
- Gene constraint
- LOEUF 0.34 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.28
- Residue 429
- the c-type lectin domain; a disulfide bond
Similar variants
- CLEC18B c.1212-212G>T Uncertain significance ★ ⚠ same type
- CLEC18B p.Ala115Val Uncertain significance ★ ⚠ same type
- CLEC18B p.Ala137Ser Uncertain significance ★ ⚠ same type
- CLEC18B p.Ala137Thr Uncertain significance ★ ⚠ same type
- CLEC18B p.Ala137Val Uncertain significance ★ ⚠ same type
- CLEC18B p.Ala19Asp Uncertain significance ★ ⚠ same type
- CLEC18B p.Ala202Val Uncertain significance ★ ⚠ same type
- CLEC18B p.Ala66Glu 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/clec18b-p-arg429cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown