INTS8 p.His922=
c.2766T>C · rs34558403 · VCV720658
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.957%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.22 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.59 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -0.054 | GERP -2.4, phastCons 0.9 |
| Overall | ||
| CADD | 5.827 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.957%
African / African-American · 718/74,998 alleles
Filtering AF
0.899%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.876%
Overall
0.0488%
786/1,611,834 alleles · rare
exomes 389/1,459,498 · genomes 397/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.957% | 104 |
| Remaining individualsnot grpmax-eligible | 0.0512% | 1,951 |
| Middle Eastern | 0.0496% | 2,016 |
| Admixed American | 0.0367% | 2,727 |
| South Asian | 0.0088% | 11,367 |
| European (non-Finnish) | 0.000255% | 392,801 |
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
- INTS8
- Protein
- p.His922=
- Coding
- c.2766T>C
- MANE Select
- NM_017864
- dbSNP
- rs34558403
- Type
- single nucleotide variant
- Location
- chr8:94876224 (GRCh38)
- Gene constraint
- LOEUF 0.453 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.47 · 10 PDB
Similar variants
- INTS8 p.Tyr499Cys Uncertain significance ★★ ⚠ same type
- INTS8 c.1018-11G>A Benign ★★ same type
- INTS8 p.Ala898= Benign ★★ same type
- INTS8 p.Gly437Glu Likely benign ★★ same type
- INTS8 p.Ser710= Benign ★★ same type
- INTS8 p.Ser755Arg Benign/Likely benign ★★ ⚠ same type
- INTS8 p.Arg359Ter Likely pathogenic ★ same type
- INTS8 c.2762+1G>A 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/ints8-p-his922 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown