INTS9 p.Leu309=
c.927G>A · rs138901254 · VCV2658508
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.978%, sas)
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 0.6 | GERP 0.84, phastCons 1 |
| Overall | ||
| CADD | 8.581 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.978%
South Asian · 891/91,064 alleles
Filtering AF
0.925%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.904%
Overall
0.566%
9,129/1,613,970 alleles · rare
exomes 8,527/1,461,728 · genomes 602/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.978% | 102 |
| Middle Eastern | 0.825% | 121 |
| European (non-Finnish) | 0.637% | 157 |
| Remaining individualsnot grpmax-eligible | 0.478% | 209 |
| Admixed American | 0.395% | 253 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| Finnishnot grpmax-eligible | 0.0828% | 1,208 |
| African / African-American | 0.0787% | 1,271 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0608% | 1,645 |
| East Asian | 0.00223% | 44,880 |
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
- INTS9
- Protein
- p.Leu309=
- Coding
- c.927G>A
- MANE Select
- NM_018250
- dbSNP
- rs138901254
- Type
- single nucleotide variant
- Location
- chr8:28793917 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.95 · 15 PDB
- Residue 309
- an α-helix
Similar variants
- INTS9 p.Leu417Pro Uncertain significance ★★ ⚠ same type
- INTS9 p.Ala208Val Uncertain significance ★ ⚠ same type
- INTS9 p.Ala286Asp Uncertain significance ★ ⚠ same type
- INTS9 p.Ala319Val Uncertain significance ★ ⚠ same type
- INTS9 p.Ala506Thr Uncertain significance ★ ⚠ same type
- INTS9 p.Ala560Thr Uncertain significance ★ ⚠ same type
- INTS9 p.Arg401Cys Uncertain significance ★ ⚠ same type
- INTS9 p.Arg401His 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/ints9-p-leu309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown