DENND5A p.Pro565=
c.1695T>G · VCV4719500
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 2.2 | phastCons 1 |
| Overall | ||
| CADD | 9.914 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,982 alleles
Overall
0.000124%
2/1,613,338 alleles · very rare
exomes 1/1,461,176 · genomes 1/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,982 |
| European (non-Finnish) | 8.48e-05% | 1,179,478 |
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
- DENND5A
- Protein
- p.Pro565=
- Coding
- c.1695T>G
- MANE Select
- NM_015213
- Type
- single nucleotide variant
- Location
- chr11:9178343 (GRCh38)
- Gene constraint
- LOEUF 0.574 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.74
- Residue 565
- the ddenn domain
Similar variants
- DENND5A p.Pro565Ser Uncertain significance ★ ⚠ same residue
- DENND5A c.949+1G>A Likely pathogenic ★★ same type
- DENND5A p.Arg772Ter Pathogenic/Likely pathogenic ★★ same type
- DENND5A p.Ala355Pro Uncertain significance ★★ ⚠ same type
- DENND5A p.Arg1159Trp Uncertain significance ★★ ⚠ same type
- DENND5A p.Arg1265His Uncertain significance ★★ ⚠ same type
- DENND5A p.Arg190His Uncertain significance ★★ ⚠ same type
- DENND5A p.Arg198Leu 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/dennd5a-p-pro565 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown