INTS11 p.Leu378=
c.1132C>T · VCV3777810
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.486%, 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 4.9 | GERP 0.034, phastCons 1 |
| Overall | ||
| CADD | 15.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.486%
European (non-Finnish) · 5,726/1,179,124 alleles
Filtering AF
0.475%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.471%
Overall
0.381%
6,139/1,611,684 alleles · rare
exomes 5,754/1,459,290 · genomes 385/152,394 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.486% | 206 |
| Remaining individualsnot grpmax-eligible | 0.354% | 282 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| Admixed American | 0.197% | 509 |
| Middle Eastern | 0.149% | 673 |
| African / African-American | 0.06% | 1,668 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0203% | 4,930 |
| Finnishnot grpmax-eligible | 0.0144% | 6,954 |
| South Asian | 0.00329% | 30,356 |
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.Leu378=
- Coding
- c.1132C>T
- MANE Select
- NM_017871
- Type
- single nucleotide variant
- Location
- chr1:1312949 (GRCh38)
- Gene constraint
- LOEUF 1.223 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.82 · 15 PDB
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-leu378 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown