INTS1 p.Ala1181=
c.3543C>T · rs73275942 · VCV781895
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 9.16%, afr) — too common for a highly-penetrant pathogenic allele
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 · G>T here scores Δ0.99 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -2.3 |
| Overall | ||
| CADD | 0.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.16%
African / African-American · 6,874/75,054 alleles
Filtering AF
8.98%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.9%
Overall
0.588%
9,473/1,612,358 alleles · common
exomes 5,321/1,460,020 · genomes 4,152/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.16% | 11 |
| Ashkenazi Jewishnot grpmax-eligible | 2.62% | 38 |
| Remaining individualsnot grpmax-eligible | 0.951% | 105 |
| Admixed American | 0.864% | 116 |
| Middle Eastern | 0.677% | 148 |
| European (non-Finnish) | 0.0522% | 1,915 |
| South Asian | 0.0505% | 1,980 |
| East Asian | 0.0134% | 7,479 |
| Finnishnot grpmax-eligible | 0.00478% | 20,907 |
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.Ala1181=
- Coding
- c.3543C>T
- MANE Select
- NM_001080453
- dbSNP
- rs73275942
- Type
- single nucleotide variant
- Location
- chr7:1482706 (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-ala1181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown