INTS1 p.Leu2088=
c.6262C>T · rs376165628 · VCV3234163
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0952%, nfe)
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 2.5 | GERP -0.64, phastCons 1 |
| Overall | ||
| CADD | 5.859 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0952%
European (non-Finnish) · 1,107/1,162,916 alleles
Filtering AF
0.0905%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0886%
Overall
0.0734%
1,157/1,577,004 alleles · ultra-rare
exomes 1,055/1,424,746 · genomes 102/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0952% | 1,051 |
| Remaining individualsnot grpmax-eligible | 0.0409% | 2,446 |
| African / African-American | 0.027% | 3,703 |
| Finnishnot grpmax-eligible | 0.00501% | 19,956 |
| Admixed American | 0.00366% | 27,322 |
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.Leu2088=
- Coding
- c.6262C>T
- MANE Select
- NM_001080453
- dbSNP
- rs376165628
- Type
- single nucleotide variant
- Location
- chr7:1471218 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
- Residue 2088
- an α-helix; a UniProt-annotated variant site (in ndcagf; decreased protein abundance); a UniProt-annotated variant site (in ndcagf)
Similar variants
- 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
- INTS1 p.Ala1854Val 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-leu2088 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown