Is KMT2D p.Pro62= (c.186G>A) pathogenic?

KMT2D p.Pro62= (c.186G>A) is classified Benign/Likely benign in KMT2D (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0446%, eas); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Pro62= (c.186G>A)?

KMT2D p.Pro62= (c.186G>A) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Pro62= (c.186G>A) in the general population?

KMT2D p.Pro62= (c.186G>A) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

KMT2D p.Pro62=

c.186G>A · rs367774720 · VCV2079687

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

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 -1.6	GERP -4.4
Overall
CADD	6.864	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0446% East Asian · 20/44,870 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00161% 26/1,613,798 alleles · ultra-rare exomes 23/1,461,500 · genomes 3/152,298 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,244
Admixed American	0.005%	20,003
European (non-Finnish)	0.000254%	393,255

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.Pro62=
Coding: c.186G>A
MANE Select: NM_003482
dbSNP: rs367774720
Type: single nucleotide variant
Location: chr12:49054742 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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.Pro62Leu Conflicting classifications of pathogenicity ★ ⚠ 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
KMT2D p.Arg1903Ter 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-pro62 (accessed [today's date]).

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