Is KMT2D p.Gly1826Val (c.5477G>T) pathogenic?

KMT2D p.Gly1826Val (c.5477G>T) is classified Benign in KMT2D (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.076); Rare (popmax 0.745%, sas); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Gly1826Val (c.5477G>T)?

KMT2D p.Gly1826Val (c.5477G>T) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Gly1826Val (c.5477G>T) in the general population?

KMT2D p.Gly1826Val (c.5477G>T) is rare (popmax 0.745%, sas) (gnomAD).

What do computational predictors say about KMT2D p.Gly1826Val (c.5477G>T)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

KMT2D p.Gly1826Val

c.5477G>T · rs574989512 · VCV134679

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.745%, sas)

Conditions

Kabuki syndrome

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.379	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.60	acceptor gain · deltas
Pangolin	Δ0.25	gain · loss 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,116 bp · p 1e-09 · regional, not allelic
Overall
CADD	24.6	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 0.745% South Asian · 679/91,082 alleles

Filtering AF 0.699% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.68%

Overall 0.0438% 707/1,613,920 alleles · rare exomes 649/1,461,638 · genomes 58/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.745%	134
Remaining individualsnot grpmax-eligible	0.0336%	2,975
Middle Eastern	0.0165%	6,062
African / African-American	0.00533%	18,756
European (non-Finnish)	0.00017%	589,918

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.Gly1826Val
Coding: c.5477G>T
MANE Select: NM_003482
dbSNP: rs574989512
Type: single nucleotide variant
Location: chr12:49043419 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1826: 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.Gly1826Ala 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
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-gly1826val (accessed [today's date]).

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