DCAF6 p.Ser520Pro
c.1558T>C · VCV3499916
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.109%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.063 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 63 kb · p 0.0024 · regional, not allelic |
| Overall | ||
| CADD | 23.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.109%
African / African-American · 82/74,902 alleles
Filtering AF
0.0904%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0833%
Overall
0.00582%
94/1,613,968 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.109% | 913 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| Admixed American | 0.00333% | 29,995 |
| South Asian | 0.0022% | 45,541 |
| European (non-Finnish) | 0.000424% | 236,002 |
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
- DCAF6
- Protein
- p.Ser520Pro
- Coding
- c.1558T>C
- MANE Select
- NM_001198956
- Type
- single nucleotide variant
- Location
- chr1:168022996 (GRCh38)
- Gene constraint
- LOEUF 0.567 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 64.23 · 1 PDB
- Residue 520
- the 'disordered' region
Similar variants
- DCAF6 p.Thr644Ile Benign ★★ same type
- ADCY10 c.292+6G>A Uncertain significance ★ same type
- ADCY10 p.Gln283His Uncertain significance ★ ⚠ same type
- ADCY10 p.Glu7Val Uncertain significance ★ ⚠ same type
- ADCY10 p.Met237Thr Uncertain significance ★ ⚠ same type
- ADCY10 p.Thr235Ser Uncertain significance ★ ⚠ same type
- ADCY10 p.Thr254Met Conflicting classifications of pathogenicity ★ ⚠ same type
- DCAF6 p.Ala295Val 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/dcaf6-p-ser520pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown