Is KMT2A p.Ala599Pro (c.1795G>C) pathogenic?

KMT2A p.Ala599Pro (c.1795G>C) is classified Uncertain significance in KMT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-07). AlphaMissense: likely benign (0.0818); Absent from gnomAD v4.1.

How common is KMT2A p.Ala599Pro (c.1795G>C) in the general population?

KMT2A p.Ala599Pro (c.1795G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KMT2A p.Ala599Pro (c.1795G>C)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

KMT2A p.Ala599Pro

c.1795G>C · VCV3695203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 508 bp · p 3.9e-10 · regional, not allelic
Overall
CADD	18.27	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: KMT2A
Protein: p.Ala599Pro
Coding: c.1795G>C
MANE Select: NM_001197104
Type: single nucleotide variant
Location: chr11:118472954 (GRCh38)
Gene constraint: LOEUF 0.065 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full KMT2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KMT2A p.Ala599Val Uncertain significance ★ ⚠ same residue
KMT2A p.Ala599= Likely benign ★ same residue
KMT2A c.10835+1G>A Likely pathogenic ★★ same type
KMT2A c.11071+1G>A Pathogenic ★★ same type
KMT2A c.4012+1G>C Pathogenic ★★ same type
KMT2A c.502+1G>A Pathogenic ★★ same type
KMT2A c.6079+2T>C Likely pathogenic ★★ same type
KMT2A p.Arg1064Ter Pathogenic ★★ same type

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/kmt2a-p-ala599pro (accessed [today's date]).

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