Is KMT2D p.Ser807Tyr (c.2420C>A) pathogenic?

KMT2D p.Ser807Tyr (c.2420C>A) is classified Benign/Likely benign in KMT2D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-24). AlphaMissense: likely benign (0.1344); Very rare (popmax 0.00603%, amr); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Ser807Tyr (c.2420C>A)?

KMT2D p.Ser807Tyr (c.2420C>A) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Ser807Tyr (c.2420C>A) in the general population?

KMT2D p.Ser807Tyr (c.2420C>A) is very rare (popmax 0.00603%, amr) (gnomAD).

What do computational predictors say about KMT2D p.Ser807Tyr (c.2420C>A)?

AlphaMissense predicts likely benign (score 0.1344) — an in-silico prediction, not a clinical call.

KMT2D p.Ser807Tyr

c.2420C>A · rs757089451 · VCV1600365

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1344 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00603%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Kabuki syndrome

Computational evidence

Protein change
AlphaMissense	0.1344	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 0.94
Regional constraint	o/e 1.01	unconstrained · MANE · 2,394 bp · p 0.74 · regional, not allelic
Overall
CADD	17.3	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 0.00603% Admixed American · 3/49,782 alleles

Filtering AF 0.0016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000843%

Overall 0.00104% 16/1,540,460 alleles · very rare exomes 16/1,389,986 · genomes 0/150,474 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00603%	16,594
Remaining individualsnot grpmax-eligible	0.00169%	59,242
African / African-American	0.00139%	72,010
European (non-Finnish)	0.000962%	103,901

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.Ser807Tyr
Coding: c.2420C>A
MANE Select: NM_003482
dbSNP: rs757089451
Type: single nucleotide variant
Location: chr12:49051263 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 807: 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.Ser807= Likely benign ★ same residue
KMT2D p.Ser807_Glu811del 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

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-ser807tyr (accessed [today's date]).

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