INTS1 p.Leu2063=
c.6189G>A · rs73267808 · VCV773884
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 4.96%, afr)
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 0.62 | GERP 0.25, phastCons 0.97 |
| Overall | ||
| CADD | 1.937 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.96%
African / African-American · 3,716/74,918 alleles
Filtering AF
4.83%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.77%
Overall
0.262%
4,221/1,612,144 alleles · low-frequency
exomes 2,136/1,459,952 · genomes 2,085/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.96% | 20 |
| Remaining individualsnot grpmax-eligible | 0.355% | 281 |
| Middle Eastern | 0.297% | 337 |
| Admixed American | 0.248% | 403 |
| South Asian | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00865% | 11,566 |
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.Leu2063=
- Coding
- c.6189G>A
- MANE Select
- NM_001080453
- dbSNP
- rs73267808
- Type
- single nucleotide variant
- Location
- chr7:1471637 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.49 · 8 PDB
- Residue 2063
- an α-helix; a UniProt-annotated variant site (in ndcagf; decreased protein abundance); a UniProt-annotated variant site (in ndcagf)
Similar variants
- 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
- INTS1 p.Ala1854Val 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-leu2063 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown