KMT2D p.Pro741=
c.2223G>C · rs374923646 · VCV2054316
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00402%, 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 -16 | GERP -2.5 |
| Overall | ||
| CADD | 0.114 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00402%
African / African-American · 3/74,598 alleles
Filtering AF
0.00107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000496%
Overall
0.000682%
11/1,612,678 alleles · very rare
exomes 7/1,461,350 · genomes 4/151,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00402% | 24,866 |
| European (non-Finnish) | 0.000678% | 147,438 |
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.Pro741=
- Coding
- c.2223G>C
- MANE Select
- NM_003482
- dbSNP
- rs374923646
- Type
- single nucleotide variant
- Location
- chr12:49051460 (GRCh38)
- Gene constraint
- LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 741
- a UniProt-annotated variant site (in kabuk1); the 'disordered' region
Similar variants
- KMT2D p.Pro741Leu Conflicting classifications of pathogenicity ★ ⚠ 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
- KMT2D p.Arg1903Ter 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-pro741 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown