INTS1 p.Thr1402=
c.4206G>A · VCV4533523
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0225%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -2.8 |
| Overall | ||
| CADD | 0.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0225%
South Asian · 19/84,374 alleles
Filtering AF
0.0147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0122%
Overall
0.00605%
94/1,554,180 alleles · ultra-rare
exomes 87/1,401,982 · genomes 7/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0225% | 4,441 |
| Remaining individualsnot grpmax-eligible | 0.00663% | 15,089 |
| European (non-Finnish) | 0.00591% | 16,925 |
| African / African-American | 0.00273% | 36,660 |
| Admixed American | 0.00192% | 51,974 |
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.Thr1402=
- Coding
- c.4206G>A
- MANE Select
- NM_001080453
- Type
- single nucleotide variant
- Location
- chr7:1479553 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
- Residue 1402
- an α-helix
Similar variants
- INTS1 p.Thr1402Met 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-thr1402 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown