INTS1 p.Ala1753=
c.5259C>T · rs375794790 · VCV2673094
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0659%, afr)
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 -15 | GERP -3 |
| Overall | ||
| CADD | 0.064 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0659%
African / African-American · 49/74,362 alleles
Filtering AF
0.0511%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0459%
Overall
0.00677%
107/1,579,424 alleles · ultra-rare
exomes 77/1,427,086 · genomes 30/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0659% | 1,518 |
| Admixed American | 0.018% | 5,546 |
| Remaining individualsnot grpmax-eligible | 0.00653% | 15,323 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00345% | 29,016 |
| European (non-Finnish) | 0.00343% | 29,138 |
| East Asian | 0.00232% | 43,068 |
| Finnishnot grpmax-eligible | 0.00174% | 57,316 |
| South Asian | 0.00116% | 86,438 |
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.Ala1753=
- Coding
- c.5259C>T
- MANE Select
- NM_001080453
- dbSNP
- rs375794790
- Type
- single nucleotide variant
- Location
- chr7:1476348 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
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-ala1753 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown