CD40 p.Lys220=
c.660G>A · VCV4839351
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00944%, amr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.284 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing |
| Pangolin | Δ0.22 | loss · gain 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 7.978 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00944%
Admixed American · 5/52,958 alleles
Filtering AF
0.00371%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0024%
Overall
0.000887%
13/1,465,456 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00944% | 10,592 |
| Finnishnot grpmax-eligible | 0.00343% | 29,113 |
| South Asian | 0.00231% | 43,276 |
| African / African-American | 0.00163% | 61,188 |
| European (non-Finnish) | 0.00028% | 357,627 |
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
- CD40
- Protein
- p.Lys220=
- Coding
- c.660G>A
- MANE Select
- NM_001250
- Type
- single nucleotide variant
- Location
- chr20:46128343 (GRCh38)
- Gene constraint
- LOEUF 0.677 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 81.10 · 14 PDB
Similar variants
- CD40 p.Ala25Ser Uncertain significance ★★ ⚠ same condition
- CD40 p.Ile204Val Uncertain significance ★★ ⚠ same condition
- CD40 p.Pro260Ser Uncertain significance ★★ ⚠ same condition
- CD40 p.Ser245Cys Uncertain significance ★★ ⚠ same condition
- CD40 p.Ser245Phe Uncertain significance ★★ ⚠ same condition
- CD40 p.Thr112Lys Uncertain significance ★★ ⚠ same condition
- CD40 p.Thr112Met Uncertain significance ★★ ⚠ same condition
- CD40 p.Val138Ala 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/cd40-p-lys220 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown