Is KMT2D p.Asp2009Val (c.6026A>T) pathogenic?

KMT2D p.Asp2009Val (c.6026A>T) is classified Uncertain significance in KMT2D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome.

How common is KMT2D p.Asp2009Val (c.6026A>T) in the general population?

KMT2D p.Asp2009Val (c.6026A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KMT2D p.Asp2009Val (c.6026A>T)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

KMT2D p.Asp2009Val

Q: What condition is associated with KMT2D p.Asp2009Val (c.6026A>T)?

KMT2D p.Asp2009Val (c.6026A>T) is associated with choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, Kabuki syndrome 1 (ClinVar).

c.6026A>T · VCV3574794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic · top 2% in KMT2D
REVEL	0.733	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.87 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,116 bp · p 1e-09 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KMT2D
Protein: p.Asp2009Val
Coding: c.6026A>T
MANE Select: NM_003482
Type: single nucleotide variant
Location: chr12:49042172 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2009: a UniProt-annotated variant site (in kabuk1)

Full KMT2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

choanal atresia-athelia-hypothyroidism-delayed puberty-short stature 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 p.Ala3541Pro Pathogenic/Likely pathogenic ★★ same condition
KMT2D p.Arg1702Ter 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-asp2009val (accessed [today's date]).

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