KMT2B p.Leu1237=
c.3711G>A · rs111726564 · VCV1649164
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.66%, 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 1.1 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 7.558 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.66%
Middle Eastern · 40/6,062 alleles
Filtering AF
0.498%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.442%
Overall
0.0235%
378/1,610,944 alleles · rare
exomes 284/1,458,588 · genomes 94/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.66% | 152 |
| African / African-American | 0.185% | 540 |
| Remaining individualsnot grpmax-eligible | 0.0881% | 1,136 |
| Admixed American | 0.0583% | 1,715 |
| European (non-Finnish) | 0.00881% | 11,345 |
| South Asian | 0.00549% | 18,218 |
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
- KMT2B
- Protein
- p.Leu1237=
- Coding
- c.3711G>A
- MANE Select
- NM_014727
- dbSNP
- rs111726564
- Type
- single nucleotide variant
- Location
- chr19:35725547 (GRCh38)
- Gene constraint
- LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1237
- a UniProt-annotated variant site (in dyt28)
Similar variants
- KMT2B p.Ala1616Val Likely pathogenic ★★ same type
- KMT2B p.Ala2641Thr Likely pathogenic ★★ same type
- KMT2B p.Arg142Ter Pathogenic ★★ same type
- KMT2B p.Arg1597Trp Pathogenic/Likely pathogenic ★★ same type
- KMT2B p.Arg1705Ter Pathogenic ★★ same type
- KMT2B p.Arg2565Gly Likely pathogenic ★★ same type
- KMT2B p.Arg2610Cys Likely pathogenic ★★ same type
- KMT2B p.Arg545Ter Pathogenic/Likely pathogenic ★★ 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/kmt2b-p-leu1237 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown