Is KMT2D p.Pro4909fs (c.14726del) pathogenic?

KMT2D p.Pro4909fs (c.14726del) is classified Pathogenic in KMT2D (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-23). No allele count reported in gnomAD v4.1 (AN 1,547,148); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Pro4909fs (c.14726del)?

KMT2D p.Pro4909fs (c.14726del) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Pro4909fs (c.14726del) in the general population?

KMT2D p.Pro4909fs (c.14726del) is no allele count reported in gnomAD v4.1 (AN 1,547,148) (gnomAD).

KMT2D p.Pro4909fs

c.14726del · rs2499039928 · VCV2102750

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,547,148)

Conditions

Kabuki syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 49 of 55
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.4	GERP -4.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,547,148). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KMT2D
Protein: p.Pro4909fs
Coding: c.14726del
MANE Select: NM_003482
dbSNP: rs2499039928
Type: Deletion
Location: chr12:49027240 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 4909: a UniProt-annotated variant site (in kabuk1); the 'disordered' region

Full KMT2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Kabuki syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KMT2D p.Ala3808fs Pathogenic/Likely pathogenic ★★ same condition
KMT2D p.Arg845fs Pathogenic ★★ same condition
KMT2D p.Asn5480fs Pathogenic ★★ same condition
KMT2D p.Asp1876fs Pathogenic/Likely pathogenic ★★ same condition
KMT2D p.Gln3796fs Pathogenic ★★ same condition
KMT2D p.Gly1235fs Pathogenic ★★ same condition
KMT2D p.Ile1509fs Pathogenic ★★ same condition
KMT2D p.Ile4440fs 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-pro4909fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown