KMT2D p.Pro628=
c.1884A>G · rs1488171868 · VCV1969977
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00153%, nfe)
Conditions
1
Kabuki syndrome
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 -0.5 | GERP -4.4, phastCons 0.084 |
| Overall | ||
| CADD | 7.925 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00153%
European (non-Finnish) · 18/1,176,312 alleles
Filtering AF
0.000956%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000789%
Overall
0.00112%
18/1,604,746 alleles · very rare
exomes 17/1,460,236 · genomes 1/144,510 · 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.Pro628=
- Coding
- c.1884A>G
- MANE Select
- NM_003482
- dbSNP
- rs1488171868
- Type
- single nucleotide variant
- Location
- chr12:49051799 (GRCh38)
- Gene constraint
- LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 628
- a UniProt-annotated variant site (in kabuk1); the 'disordered' region; the '15 x 5 aa repeats of s/p-p-p-e/p-e/a' 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-pro628 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown