INTS1 p.Ala1235=
c.3705C>G · rs200579639 · VCV3045516
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.017%, nfe)
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 1.6 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 9.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.017%
European (non-Finnish) · 200/1,176,988 alleles
Filtering AF
0.0151%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0143%
Overall
0.0131%
210/1,607,248 alleles · ultra-rare
exomes 193/1,455,008 · genomes 17/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.017% | 5,885 |
| Remaining individualsnot grpmax-eligible | 0.00803% | 12,457 |
| Finnishnot grpmax-eligible | 0.00492% | 20,323 |
| Admixed American | 0.00167% | 59,894 |
| African / African-American | 0.00133% | 74,926 |
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.Ala1235=
- Coding
- c.3705C>G
- MANE Select
- NM_001080453
- dbSNP
- rs200579639
- Type
- single nucleotide variant
- Location
- chr7:1481487 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
- Residue 1235
- an α-helix
Similar variants
- INTS1 p.Ala1235Thr 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-ala1235 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown