Is KMT2A p.Val1237Leu (c.3709G>C) pathogenic?

KMT2A p.Val1237Leu (c.3709G>C) is classified Likely benign in KMT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely benign (0.0705); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KMT2A p.Val1237Leu (c.3709G>C)?

KMT2A p.Val1237Leu (c.3709G>C) is associated with Inborn genetic diseases (ClinVar).

How common is KMT2A p.Val1237Leu (c.3709G>C) in the general population?

KMT2A p.Val1237Leu (c.3709G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about KMT2A p.Val1237Leu (c.3709G>C)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

KMT2A p.Val1237Leu

c.3709G>C · VCV4623055

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.111	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 -1.1	GERP -3.7
Regional constraint	o/e 0.78	unconstrained · MANE · 2,556 bp · p 0.0011 · regional, not allelic
Overall
CADD	0.15	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 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,870 alleles · very rare

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: KMT2A
Protein: p.Val1237Leu
Coding: c.3709G>C
MANE Select: NM_001197104
Type: single nucleotide variant
Location: chr11:118481789 (GRCh38)
Gene constraint: LOEUF 0.065 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1237: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KMT2A p.Val1237Met Uncertain significance ★ ⚠ same residue
KMT2A p.Arg1101Ter Pathogenic/Likely pathogenic ★★ same condition
KMT2A p.Arg1151Ter Pathogenic ★★ same condition
KMT2A p.Arg1264Ter Pathogenic ★★ same condition
KMT2A p.Arg1502Ter Pathogenic ★★ same condition
KMT2A p.Arg1963Ter Pathogenic/Likely pathogenic ★★ same condition
KMT2A p.Arg1979Ter Pathogenic ★★ same condition
KMT2A p.Arg2163Ter 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/kmt2a-p-val1237leu (accessed [today's date]).

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