Is KMT2D p.Ile2026Val (c.6076A>G) pathogenic?

KMT2D p.Ile2026Val (c.6076A>G) is classified Benign/Likely benign in KMT2D (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.1251); Low-frequency (popmax 1.34%, afr); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Ile2026Val (c.6076A>G)?

KMT2D p.Ile2026Val (c.6076A>G) is associated with Kabuki syndrome, Kabuki syndrome 1 (ClinVar).

How common is KMT2D p.Ile2026Val (c.6076A>G) in the general population?

KMT2D p.Ile2026Val (c.6076A>G) is low-frequency (popmax 1.34%, afr) (gnomAD).

What do computational predictors say about KMT2D p.Ile2026Val (c.6076A>G)?

AlphaMissense predicts likely benign (score 0.1251) — an in-silico prediction, not a clinical call.

KMT2D p.Ile2026Val

c.6076A>G · rs190995850 · VCV500446

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1251 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, afr)

Conditions

Kabuki syndrome

Computational evidence

Protein change
AlphaMissense	0.1251	likely benign
REVEL	0.327	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,116 bp · p 1e-09 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.34% African / African-American · 1,008/75,026 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0677% 1,092/1,613,738 alleles · low-frequency exomes 536/1,461,474 · genomes 556/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.34%	74
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Admixed American	0.0417%	2,400
Middle Eastern	0.0165%	6,060
East Asian	0.00223%	44,880
European (non-Finnish)	0.00119%	84,269

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.Ile2026Val
Coding: c.6076A>G
MANE Select: NM_003482
dbSNP: rs190995850
Type: single nucleotide variant
Location: chr12:49042122 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2026: a UniProt-annotated variant site (in kabuk1)

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

Also linked: Kabuki syndrome 1

Similar variants

KMT2D c.10740+1G>A Pathogenic ★★ same condition
KMT2D c.14075+1G>A Pathogenic/Likely pathogenic ★★ same condition
KMT2D c.14251+1G>C Likely pathogenic ★★ same condition
KMT2D c.16338+1G>T Pathogenic/Likely pathogenic ★★ same condition
KMT2D c.16338+2T>C Pathogenic/Likely pathogenic ★★ same condition
KMT2D c.177-2A>G 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-ile2026val (accessed [today's date]).

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