DLK1 p.Pro280=
c.840G>A · rs35339877 · VCV786626
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 9.51%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.29 | GERP -3, phastCons 0.12 |
| Overall | ||
| CADD | 8.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.51%
African / African-American · 7,130/74,976 alleles
Filtering AF
9.33%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.25%
Overall
0.515%
8,308/1,613,646 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.51% | 11 |
| Admixed American | 0.951% | 105 |
| Remaining individualsnot grpmax-eligible | 0.622% | 161 |
| Middle Eastern | 0.33% | 303 |
| European (non-Finnish) | 0.0158% | 6,310 |
| South Asian | 0.011% | 9,107 |
| East Asian | 0.00223% | 44,866 |
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
- DLK1
- Protein
- p.Pro280=
- Coding
- c.840G>A
- MANE Select
- NM_003836
- dbSNP
- rs35339877
- Type
- single nucleotide variant
- Location
- chr14:100734584 (GRCh38)
- Gene constraint
- LOEUF 0.461 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 70.55 · 1 PDB
Similar variants
- DLK1 p.Arg344Gln Uncertain significance ★★ ⚠ same type
- DLK1 p.Ala213Thr Likely benign ★★ same type
- DLK1 p.Asp380His Benign ★★ same type
- DLK1 p.Gln33= Benign/Likely benign ★★ same type
- DLK1 p.Gln73Leu Benign ★★ same type
- DLK1 p.Ser375= Benign ★★ same type
- DLK1 p.Thr321= Likely benign ★★ same type
- DLK1 p.Val104Met Benign ★★ 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/dlk1-p-pro280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown