DIAPH3 p.Pro580=
c.1740A>G · rs748308779 · VCV2807815
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 -5.8 | GERP -3.2 |
| Overall | ||
| CADD | 1.299 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,916 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000616%
9/1,461,484 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,916 |
| South Asian | 0.0011% | 91,002 |
| European (non-Finnish) | 0.000593% | 168,530 |
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.Pro580=
- Coding
- c.1740A>G
- MANE Select
- NM_001042517
- dbSNP
- rs748308779
- Type
- single nucleotide variant
- Location
- chr13:59971071 (GRCh38)
- Gene constraint
- LOEUF 0.889 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.33 · 2 PDB
- Residue 580
- the fh1 domain; the 'disordered' region
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-pro580 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown