Is KMT2D p.Arg65= (c.195T>C) pathogenic?

KMT2D p.Arg65= (c.195T>C) is classified Benign in KMT2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-08). Very rare (popmax 6.2e-05%); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Arg65= (c.195T>C)?

KMT2D p.Arg65= (c.195T>C) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Arg65= (c.195T>C) in the general population?

KMT2D p.Arg65= (c.195T>C) is very rare (popmax 6.2e-05%) (gnomAD).

KMT2D p.Arg65=

c.195T>C · rs1250596620 · VCV2030114

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

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 0.14	GERP -4.4, phastCons 0.061
Overall
CADD	5.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,792 alleles · very rare exomes 1/1,461,540 · genomes 0/152,252 · joint denominator

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.Arg65=
Coding: c.195T>C
MANE Select: NM_003482
dbSNP: rs1250596620
Type: single nucleotide variant
Location: chr12:49054733 (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.Arg65Cys Conflicting classifications of pathogenicity ★ same residue
KMT2D p.Arg65Ser Uncertain significance ★ same residue
KMT2D p.Arg65His 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

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-arg65 (accessed [today's date]).

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