INTS1 p.Leu972=
c.2916G>A · VCV4894952
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0266%, 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 -3.1 | GERP -1.9 |
| Overall | ||
| CADD | 2.697 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0266%
African / African-American · 20/75,066 alleles
Filtering AF
0.0176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.00192%
31/1,612,548 alleles · ultra-rare
exomes 27/1,460,182 · genomes 4/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0266% | 3,753 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,937 |
| Admixed American | 0.00167% | 59,968 |
| European (non-Finnish) | 8.48e-05% | 1,179,775 |
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.Leu972=
- Coding
- c.2916G>A
- MANE Select
- NM_001080453
- Type
- single nucleotide variant
- Location
- chr7:1486685 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
- Residue 972
- an α-helix
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-leu972 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown