Is KMT2D p.Ser1237= (c.3711C>T) pathogenic?

KMT2D p.Ser1237= (c.3711C>T) is classified Likely benign in KMT2D (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). Absent from gnomAD v4.1; Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Ser1237= (c.3711C>T)?

KMT2D p.Ser1237= (c.3711C>T) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Ser1237= (c.3711C>T) in the general population?

KMT2D p.Ser1237= (c.3711C>T) is absent from gnomAD v4.1 (gnomAD).

KMT2D p.Ser1237=

c.3711C>T · rs2120642103 · VCV1611631

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 2.7	GERP 1.2, phastCons 1
Overall
CADD	11.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KMT2D
Protein: p.Ser1237=
Coding: c.3711C>T
MANE Select: NM_003482
dbSNP: rs2120642103
Type: single nucleotide variant
Location: chr12:49049877 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1237: 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.Ser1237Phe Conflicting classifications of pathogenicity ★ same residue
KMT2D p.Ser1237Ala 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-ser1237 (accessed [today's date]).

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