Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.15%, 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 2.2 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 5.534 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.15%
African / African-American · 1,186/55,116 alleles
Filtering AF
2.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.01%
Overall
0.114%
1,337/1,169,868 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.15% | 46 |
| Remaining individualsnot grpmax-eligible | 0.169% | 590 |
| Admixed American | 0.146% | 684 |
| Middle Eastern | 0.0237% | 4,213 |
| South Asian | 0.002% | 50,049 |
| European (non-Finnish) | 0.0016% | 62,569 |
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
- DIAPH2
- Protein
- p.His754=
- Coding
- c.2262T>C
- MANE Select
- NM_006729
- dbSNP
- rs20387
- Type
- single nucleotide variant
- Location
- chrX:97099708 (GRCh38)
- Structure
- AlphaFold pLDDT 76.09
- Residue 754
- the fh2 domain
Similar variants
- DIAPH2 p.Ala83Thr Benign/Likely benign ★★ same type
- DIAPH2 p.Ile475= Likely benign ★★ same type
- DIAPH2 p.Phe504= Benign ★★ same type
- DIAPH2 c.733-1G>T Uncertain significance ★ same type
- DIAPH2 p.Ala125Val Uncertain significance ★ ⚠ same type
- DIAPH2 p.Ala488Val Uncertain significance ★ ⚠ same type
- DIAPH2 p.Ala672Thr Uncertain significance ★ ⚠ same type
- DIAPH2 p.Ala6Thr 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/diaph2-p-his754 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown