KMT2D p.Gln4635=
c.13905G>A · rs1942836641 · VCV1663629
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.69e-05%, nfe)
Conditions
1
Kabuki syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.75 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 19.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.69e-05%
European (non-Finnish) · 1/1,150,912 alleles
Overall
6.37e-05%
1/1,571,068 alleles · very rare
exomes 1/1,426,560 · genomes 0/144,508 · joint denominator
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.Gln4635=
- Coding
- c.13905G>A
- MANE Select
- NM_003482
- dbSNP
- rs1942836641
- Type
- single nucleotide variant
- Location
- chr12:49030374 (GRCh38)
- Gene constraint
- LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 4635
- a UniProt-annotated variant site (in kabuk1); the 'disordered' region
Similar variants
- 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
- KMT2D p.Arg2099Ter 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-gln4635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown