INTS11 p.Ala561=
c.1683C>T · VCV4534027
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, 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 -7.6 | GERP -3.7 |
| Overall | ||
| CADD | 0.022 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
European (non-Finnish) · 128/1,158,442 alleles
Filtering AF
0.00945%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00888%
Overall
0.00941%
148/1,573,470 alleles · ultra-rare
exomes 140/1,421,430 · genomes 8/152,040 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.011% | 9,050 |
| South Asian | 0.00925% | 10,816 |
| Remaining individualsnot grpmax-eligible | 0.0082% | 12,196 |
| African / African-American | 0.00536% | 18,653 |
| Admixed American | 0.00373% | 26,776 |
| Finnishnot grpmax-eligible | 0.00167% | 59,820 |
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.Ala561=
- Coding
- c.1683C>T
- MANE Select
- NM_017871
- Type
- single nucleotide variant
- Location
- chr1:1312072 (GRCh38)
- Gene constraint
- LOEUF 1.223 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.82 · 15 PDB
- Residue 561
- a β-strand
Similar variants
- 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
- INTS11 p.Arg196= 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-ala561 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown