INTS1 p.Leu572=
c.1716G>A · rs143689649 · VCV723612
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.784%, sas)
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 -8.7 | GERP -2.5 |
| Overall | ||
| CADD | 0.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.784%
South Asian · 711/90,636 alleles
Filtering AF
0.737%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.718%
Overall
0.27%
4,354/1,609,688 alleles · rare
exomes 4,111/1,457,348 · genomes 243/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.784% | 127 |
| European (non-Finnish) | 0.292% | 343 |
| Remaining individualsnot grpmax-eligible | 0.178% | 562 |
| Middle Eastern | 0.0827% | 1,209 |
| Finnishnot grpmax-eligible | 0.0533% | 1,876 |
| African / African-American | 0.04% | 2,500 |
| Admixed American | 0.0318% | 3,143 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00678% | 14,741 |
| East Asian | 0.00223% | 44,756 |
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.Leu572=
- Coding
- c.1716G>A
- MANE Select
- NM_001080453
- dbSNP
- rs143689649
- Type
- single nucleotide variant
- Location
- chr7:1495549 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
Similar variants
- INTS1 p.Leu572Pro 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-leu572 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown