Is KMT2D p.Ser1007Phe (c.3020C>T) pathogenic?

KMT2D p.Ser1007Phe (c.3020C>T) is classified Likely benign in KMT2D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-08). AlphaMissense: likely benign (0.1774); Very rare (popmax 0.00331%, sas); Associated with Kabuki syndrome.

What condition is associated with KMT2D p.Ser1007Phe (c.3020C>T)?

KMT2D p.Ser1007Phe (c.3020C>T) is associated with Kabuki syndrome (ClinVar).

How common is KMT2D p.Ser1007Phe (c.3020C>T) in the general population?

KMT2D p.Ser1007Phe (c.3020C>T) is very rare (popmax 0.00331%, sas) (gnomAD).

What do computational predictors say about KMT2D p.Ser1007Phe (c.3020C>T)?

AlphaMissense predicts likely benign (score 0.1774) — an in-silico prediction, not a clinical call.

KMT2D p.Ser1007Phe

c.3020C>T · VCV3713650

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1774 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00331%, sas)

Conditions

Kabuki syndrome

Computational evidence

Protein change
AlphaMissense	0.1774	likely benign
REVEL	0.379	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,944 bp · p 0.018 · regional, not allelic
Overall
CADD	21.7	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 0.00331% South Asian · 3/90,622 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000444%

Overall 0.000873% 14/1,604,302 alleles · very rare exomes 14/1,452,052 · genomes 0/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00331%	30,207
European (non-Finnish)	0.000938%	106,627

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.Ser1007Phe
Coding: c.3020C>T
MANE Select: NM_003482
Type: single nucleotide variant
Location: chr12:49050568 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1007: 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 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
KMT2D p.Arg2099Ter 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-ser1007phe (accessed [today's date]).

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