KMT2D p.Pro763=
c.2289G>A · rs529665353 · VCV1606438
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00495%, afr)
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 -15 | GERP -2 |
| Overall | ||
| CADD | 0.168 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00495%
African / African-American · 3/60,656 alleles
Filtering AF
0.00264%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00238%
Overall
0.00296%
46/1,551,792 alleles · very rare
exomes 40/1,438,326 · genomes 6/113,466 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00495% | 20,219 |
| European (non-Finnish) | 0.00356% | 28,123 |
| East Asian | 0.00239% | 41,838 |
| Finnishnot grpmax-eligible | 0.00167% | 59,848 |
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.Pro763=
- Coding
- c.2289G>A
- MANE Select
- NM_003482
- dbSNP
- rs529665353
- Type
- single nucleotide variant
- Location
- chr12:49051394 (GRCh38)
- Gene constraint
- LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 763
- a UniProt-annotated variant site (in kabuk1); the 'disordered' region
Similar variants
- KMT2D p.Pro763Leu Benign/Likely benign ★★ same residue
- KMT2D p.Pro763Ala Likely benign ★ 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
- KMT2D p.Arg1615Ter 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-pro763 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown