INTS1 p.Thr1745=
c.5235G>A · rs770264501 · VCV2657184
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0144%, amr)
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 -0.5 | GERP -3.1 |
| Overall | ||
| CADD | 0.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0144%
Admixed American · 8/55,448 alleles
Filtering AF
0.00708%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00516%
Overall
0.00152%
24/1,576,410 alleles · ultra-rare
exomes 21/1,424,174 · genomes 3/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0144% | 6,931 |
| African / African-American | 0.00539% | 18,545 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,288 |
| European (non-Finnish) | 0.000944% | 105,970 |
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.Thr1745=
- Coding
- c.5235G>A
- MANE Select
- NM_001080453
- dbSNP
- rs770264501
- Type
- single nucleotide variant
- Location
- chr7:1476372 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
- Residue 1745
- an α-helix
Similar variants
- INTS1 p.Thr1745Met 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-thr1745 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown