INTS1 p.Ser995=
c.2985G>A · rs190236314 · VCV732041
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.437%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.7 | GERP -2.8 |
| Overall | ||
| CADD | 8.143 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.437%
East Asian · 196/44,872 alleles
Filtering AF
0.387%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.367%
Overall
0.0171%
275/1,612,234 alleles · rare
exomes 250/1,459,872 · genomes 25/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.437% | 229 |
| South Asian | 0.0538% | 1,859 |
| Middle Eastern | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,939 |
| Finnishnot grpmax-eligible | 0.00321% | 31,190 |
| European (non-Finnish) | 0.00153% | 65,545 |
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
- INTS1
- Protein
- p.Ser995=
- Coding
- c.2985G>A
- MANE Select
- NM_001080453
- dbSNP
- rs190236314
- Type
- single nucleotide variant
- Location
- chr7:1485461 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
- Residue 995
- an α-helix
Similar variants
- INTS1 p.Ser995Leu Uncertain significance ★ ⚠ same residue
- INTS1 c.3430-2A>C Likely pathogenic ★★ same type
- INTS1 p.Arg101Ter Likely pathogenic ★★ same type
- INTS1 p.Glu182Ter Likely pathogenic ★★ same type
- INTS1 c.1283+5G>A Uncertain significance ★★ same type
- INTS1 c.2977-5C>T Uncertain significance ★★ same type
- INTS1 p.Ala1112Val Uncertain significance ★★ ⚠ same type
- INTS1 p.Ala1505Val 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/ints1-p-ser995 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown