Is KMT2D p.Pro385= (c.1155C>T) pathogenic?

KMT2D p.Pro385= (c.1155C>T) is classified Benign/Likely benign in KMT2D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.2%, sas); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Pro385= (c.1155C>T)?

KMT2D p.Pro385= (c.1155C>T) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Pro385= (c.1155C>T) in the general population?

KMT2D p.Pro385= (c.1155C>T) is rare (popmax 0.2%, sas) (gnomAD).

KMT2D p.Pro385=

c.1155C>T · rs545791832 · VCV309087

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.2%, sas)

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 -1.5	GERP -4.8
Overall
CADD	10.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.2% South Asian · 182/91,056 alleles

Filtering AF 0.176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.0185% 298/1,613,678 alleles · rare exomes 276/1,461,468 · genomes 22/152,210 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.2%	500
Amishnot grpmax-eligible	0.11%	912
Remaining individualsnot grpmax-eligible	0.0192%	5,205
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.00848%	11,797
Admixed American	0.00167%	59,976
African / African-American	0.00133%	74,978

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.Pro385=
Coding: c.1155C>T
MANE Select: NM_003482
dbSNP: rs545791832
Type: single nucleotide variant
Location: chr12:49052667 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 385: 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.Pro385Ser 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
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-pro385 (accessed [today's date]).

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