INTS1 p.Pro721=
c.2163G>A · VCV4894960
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.038%, eas)
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 -20 | GERP -2.3 |
| Overall | ||
| CADD | 0.002 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.038%
East Asian · 17/44,738 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.0036%
58/1,610,726 alleles · ultra-rare
exomes 48/1,459,426 · genomes 10/151,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.038% | 2,632 |
| African / African-American | 0.0174% | 5,732 |
| South Asian | 0.0033% | 30,324 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,179 |
| European (non-Finnish) | 0.00187% | 53,544 |
| Admixed American | 0.00167% | 59,902 |
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.Pro721=
- Coding
- c.2163G>A
- MANE Select
- NM_001080453
- Type
- single nucleotide variant
- Location
- chr7:1493012 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
Similar variants
- INTS1 p.Pro721Leu 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-pro721 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown