INTS1 p.Pro1364=
c.4092G>A · rs182750375 · VCV1678489
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.224%, afr)
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 -11 | GERP -2.8 |
| Overall | ||
| CADD | 0.225 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.224%
African / African-American · 157/70,202 alleles
Filtering AF
0.195%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.184%
Overall
0.0159%
234/1,470,872 alleles · rare
exomes 145/1,318,530 · genomes 89/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.224% | 447 |
| South Asian | 0.0399% | 2,506 |
| East Asian | 0.0379% | 2,635 |
| Middle Eastern | 0.0372% | 2,686 |
| Remaining individualsnot grpmax-eligible | 0.0353% | 2,834 |
| Admixed American | 0.0205% | 4,870 |
| European (non-Finnish) | 0.00027% | 369,928 |
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.Pro1364=
- Coding
- c.4092G>A
- MANE Select
- NM_001080453
- dbSNP
- rs182750375
- Type
- single nucleotide variant
- Location
- chr7:1479667 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
Similar variants
- INTS1 p.Pro1364Leu 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-pro1364 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown