DIAPH3 p.Asp399=
c.1197T>C · rs147456179 · VCV713518
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.622%, afr)
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 2.8 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 5.343 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.622%
African / African-American · 466/74,912 alleles
Filtering AF
0.575%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.557%
Overall
0.0337%
543/1,612,038 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.622% | 161 |
| Remaining individualsnot grpmax-eligible | 0.0513% | 1,949 |
| Middle Eastern | 0.0497% | 2,011 |
| Admixed American | 0.0452% | 2,215 |
| South Asian | 0.0033% | 30,346 |
| European (non-Finnish) | 0.00102% | 98,235 |
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
- DIAPH3
- Protein
- p.Asp399=
- Coding
- c.1197T>C
- MANE Select
- NM_001042517
- dbSNP
- rs147456179
- Type
- single nucleotide variant
- Location
- chr13:59992115 (GRCh38)
- Gene constraint
- LOEUF 0.889 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.33 · 2 PDB
- Residue 399
- the gbd/fh3 domain
Similar variants
- DIAPH3 p.Ala500Val Uncertain significance ★★ ⚠ same type
- DIAPH3 p.Ala546Thr Uncertain significance ★★ ⚠ same type
- DIAPH3 p.Arg1027His Uncertain significance ★★ ⚠ same type
- DIAPH3 p.Arg1048Cys Uncertain significance ★★ ⚠ same type
- DIAPH3 p.Arg1048Gly Uncertain significance ★★ ⚠ same type
- DIAPH3 p.Arg1089Pro Uncertain significance ★★ ⚠ same type
- DIAPH3 p.Arg1191Ter Uncertain significance ★★ same type
- DIAPH3 p.Arg31Gln 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/diaph3-p-asp399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown