INTS8 p.Pro166=
c.498C>T · rs750330835 · VCV743513
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.172 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.42 | GERP -2.5, phastCons 0.98 |
| Overall | ||
| CADD | 10.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,894 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000434%
7/1,613,808 alleles · very rare
exomes 6/1,461,682 · genomes 1/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,965 |
| Admixed American | 0.00167% | 59,986 |
| European (non-Finnish) | 0.000254% | 393,286 |
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.Pro166=
- Coding
- c.498C>T
- MANE Select
- NM_017864
- dbSNP
- rs750330835
- Type
- single nucleotide variant
- Location
- chr8:94827773 (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.His922= Benign ★★ same type
- INTS8 p.Ser710= Benign ★★ same type
- INTS8 p.Ser755Arg Benign/Likely benign ★★ ⚠ same type
- INTS8 p.Arg359Ter Likely pathogenic ★ 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-pro166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown