INTS11 p.Asp580=
c.1740C>T · rs146699248 · VCV720217
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.388%, mid)
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 -4.3 | GERP -3.7 |
| Overall | ||
| CADD | 0.013 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.388%
Middle Eastern · 23/5,930 alleles
Filtering AF
0.265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.252%
Overall
0.0686%
1,082/1,578,234 alleles · rare
exomes 864/1,425,924 · genomes 218/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.388% | 258 |
| African / African-American | 0.296% | 338 |
| Ashkenazi Jewishnot grpmax-eligible | 0.27% | 370 |
| Admixed American | 0.189% | 529 |
| Remaining individualsnot grpmax-eligible | 0.15% | 669 |
| East Asian | 0.135% | 739 |
| European (non-Finnish) | 0.0438% | 2,284 |
| South Asian | 0.00456% | 21,942 |
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
- INTS11
- Protein
- p.Asp580=
- Coding
- c.1740C>T
- MANE Select
- NM_017871
- dbSNP
- rs146699248
- Type
- single nucleotide variant
- Location
- chr1:1311922 (GRCh38)
- Gene constraint
- LOEUF 1.223 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.82 · 15 PDB
- Residue 580
- an α-helix
Similar variants
- INTS11 p.Asp580Ala Uncertain significance ★ ⚠ same residue
- INTS11 c.28+1406C>T Uncertain significance ★★ same type
- INTS11 p.Ala241Thr Uncertain significance ★★ ⚠ same type
- INTS11 p.Arg231Cys Uncertain significance ★★ ⚠ same type
- INTS11 p.Gln467His Uncertain significance ★★ ⚠ same type
- INTS11 p.Glu227Lys Uncertain significance ★★ same type
- INTS11 p.His157Arg Uncertain significance ★★ ⚠ same type
- INTS11 c.1607+18C>A Benign ★★ 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/ints11-p-asp580 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown