INVS p.His428=
c.1284T>C · rs77465715 · VCV260406
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.21%, afr)
Conditions
2
kidney disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -5.5 |
| Overall | ||
| CADD | 0.391 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.21%
African / African-American · 907/75,030 alleles
Filtering AF
1.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.12%
Overall
0.0647%
1,044/1,613,976 alleles · low-frequency
exomes 520/1,461,688 · genomes 524/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.21% | 83 |
| Remaining individualsnot grpmax-eligible | 0.0816% | 1,226 |
| Admixed American | 0.0583% | 1,715 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.00549% | 18,216 |
| European (non-Finnish) | 0.00364% | 27,439 |
| East Asian | 0.00223% | 44,872 |
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
- INVS
- Protein
- p.His428=
- Coding
- c.1284T>C
- MANE Select
- NM_014425
- dbSNP
- rs77465715
- Type
- single nucleotide variant
- Location
- chr9:100252956 (GRCh38)
- Gene constraint
- LOEUF 0.941 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.76
Similar variants
- INVS c.107-1G>A Likely pathogenic ★★ same condition
- INVS c.1078+1G>A Pathogenic ★★ same condition
- INVS c.1464+1G>T Pathogenic/Likely pathogenic ★★ same condition
- INVS c.2068+2T>C Likely pathogenic ★★ same condition
- INVS c.2069-1G>T Likely pathogenic ★★ same condition
- INVS c.2786+1G>A Pathogenic/Likely pathogenic ★★ same condition
- INVS c.2786+2T>C Pathogenic/Likely pathogenic ★★ same condition
- INVS c.615+1G>A Likely pathogenic ★★ same condition
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/invs-p-his428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown