Is KMT2D p.Pro710= (c.2130A>G) pathogenic?

KMT2D p.Pro710= (c.2130A>G) is classified Likely benign in KMT2D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-13). Ultra-rare (popmax 0.0148%, afr); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Pro710= (c.2130A>G)?

KMT2D p.Pro710= (c.2130A>G) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Pro710= (c.2130A>G) in the general population?

KMT2D p.Pro710= (c.2130A>G) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

KMT2D p.Pro710=

c.2130A>G · rs534199254 · VCV2166569

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Conditions

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 -1.3	GERP -2.3
Overall
CADD	2.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0148% African / African-American · 11/74,110 alleles

Filtering AF 0.00824% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00639%

Overall 0.000808% 13/1,608,806 alleles · ultra-rare exomes 7/1,458,736 · genomes 6/150,070 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0148%	6,737
Remaining individualsnot grpmax-eligible	0.00321%	31,156

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.Pro710=
Coding: c.2130A>G
MANE Select: NM_003482
dbSNP: rs534199254
Type: single nucleotide variant
Location: chr12:49051553 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 710: 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.Pro710Arg Likely benign ★★ same residue
KMT2D p.Pro710Gln Uncertain significance ★ ⚠ 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-pro710 (accessed [today's date]).

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