KMT2B p.Pro404=
c.1212G>A · rs574300657 · VCV1599858
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0765%, 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 -0.74 | GERP -3.9 |
| Overall | ||
| CADD | 0.353 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0765%
European (non-Finnish) · 875/1,144,102 alleles
Filtering AF
0.0723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0705%
Overall
0.0584%
903/1,545,124 alleles · ultra-rare
exomes 839/1,393,474 · genomes 64/151,650 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0765% | 1,308 |
| Remaining individualsnot grpmax-eligible | 0.0234% | 4,270 |
| African / African-American | 0.00966% | 10,347 |
| Admixed American | 0.00596% | 16,782 |
| Finnishnot grpmax-eligible | 0.00504% | 19,859 |
| East Asian | 0.00245% | 40,876 |
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.Pro404=
- Coding
- c.1212G>A
- MANE Select
- NM_014727
- dbSNP
- rs574300657
- Type
- single nucleotide variant
- Location
- chr19:35720559 (GRCh38)
- Gene constraint
- LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 404
- the 'disordered' region; a UniProt-annotated variant site (in dyt28)
Similar variants
- KMT2B p.Pro404Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown