Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.65%, eas)
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 -3.8 | GERP -3.6 |
| Overall | ||
| CADD | 5.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.65%
East Asian · 1,638/44,882 alleles
Filtering AF
3.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.44%
Overall
0.137%
2,210/1,614,164 alleles · low-frequency
exomes 1,965/1,461,836 · genomes 245/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 3.65% | 27 |
| Admixed American | 0.277% | 362 |
| Middle Eastern | 0.165% | 606 |
| South Asian | 0.159% | 628 |
| Remaining individualsnot grpmax-eligible | 0.139% | 719 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0743% | 1,346 |
| African / African-American | 0.044% | 2,274 |
| European (non-Finnish) | 0.00924% | 10,826 |
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
- KMT2A
- Protein
- p.Pro658=
- Coding
- c.1974C>T
- MANE Select
- NM_001197104
- dbSNP
- rs9332773
- Type
- single nucleotide variant
- Location
- chr11:118473133 (GRCh38)
- Gene constraint
- LOEUF 0.065 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Similar variants
- KMT2A p.Pro658Arg Uncertain significance ★ same residue
- KMT2A c.10835+1G>A Likely pathogenic ★★ same type
- KMT2A c.11071+1G>A Pathogenic ★★ same type
- KMT2A c.4012+1G>C Pathogenic ★★ same type
- KMT2A c.502+1G>A Pathogenic ★★ same type
- KMT2A c.6079+2T>C Likely pathogenic ★★ same type
- KMT2A p.Arg1064Ter Pathogenic ★★ same type
- KMT2A p.Arg1081Ter 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/kmt2a-p-pro658 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown