KMT2D p.Pro15=
c.45G>A · rs750506197 · VCV2916528
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Conditions
1
Kabuki syndrome
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 | GERP -4.4 |
| Overall | ||
| CADD | 8.487 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,890 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.00031%
5/1,613,874 alleles · very rare
exomes 3/1,461,664 · genomes 2/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,445 |
| Admixed American | 0.00167% | 60,012 |
| African / African-American | 0.00133% | 74,928 |
| European (non-Finnish) | 8.48e-05% | 1,179,871 |
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
- KMT2D
- Protein
- p.Pro15=
- Coding
- c.45G>A
- MANE Select
- NM_003482
- dbSNP
- rs750506197
- Type
- single nucleotide variant
- Location
- chr12:49055280 (GRCh38)
- Gene constraint
- LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 15
- the 'disordered' region
Similar variants
- KMT2D p.Pro15Ser Uncertain significance ★ ⚠ same residue
- KMT2D p.Pro15Leu Likely benign ★ same residue
- KMT2D p.Pro15Gln Uncertain significance ★ ⚠ same residue
- KMT2D c.10740+1G>A Pathogenic ★★ same condition
- KMT2D c.14075+1G>A Pathogenic/Likely pathogenic ★★ same condition
- KMT2D c.16338+2T>C Pathogenic/Likely pathogenic ★★ same condition
- KMT2D c.4132-2A>G Pathogenic ★★ same condition
- KMT2D c.5189-2A>G Pathogenic/Likely pathogenic ★★ same condition
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/kmt2d-p-pro15 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown