CCDC28B p.Asp166=
c.498C>T · VCV4965409
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00257%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.94, phastCons 1 |
| Overall | ||
| CADD | 9.285 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00257%
European (non-Finnish) · 30/1,169,500 alleles
Filtering AF
0.00182%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00158%
Overall
0.00195%
31/1,593,570 alleles · very rare
exomes 30/1,441,390 · genomes 1/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00257% | 38,983 |
| African / African-American | 0.00134% | 74,392 |
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
- CCDC28B
- Protein
- p.Asp166=
- Coding
- c.498C>T
- MANE Select
- NM_024296
- Type
- single nucleotide variant
- Location
- chr1:32204352 (GRCh38)
- Gene constraint
- LOEUF 1.357 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.15
Similar variants
- CCDC28B p.Asp166Asn Uncertain significance ★ ⚠ same residue
- CCDC28B p.Lys112= Uncertain significance ★★ same type
- CCDC28B p.Arg25Trp Benign ★★ same type
- CCDC28B p.Glu154= Benign/Likely benign ★★ same type
- CCDC28B p.Gly155Arg Benign/Likely benign ★★ same type
- CCDC28B p.Ala199Asp Uncertain significance ★ ⚠ same type
- CCDC28B p.Ala20Val Uncertain significance ★ ⚠ same type
- CCDC28B p.Ala73Pro 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/ccdc28b-p-asp166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown