Is KMT2A p.Val1237Met (c.3709G>A) pathogenic?

KMT2A p.Val1237Met (c.3709G>A) is classified Uncertain significance in KMT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-08). AlphaMissense: likely benign (0.0743); Very rare (popmax 0.00891%, eas).

How common is KMT2A p.Val1237Met (c.3709G>A) in the general population?

KMT2A p.Val1237Met (c.3709G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about KMT2A p.Val1237Met (c.3709G>A)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

KMT2A p.Val1237Met

c.3709G>A · rs572783697 · VCV2998145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.089	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	3.079	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

Grpmax group 0.00891% East Asian · 4/44,882 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000496% 8/1,614,170 alleles · very rare exomes 8/1,461,870 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
South Asian	0.0022%	45,542
European (non-Finnish)	0.000169%	590,012

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.Val1237Met
Coding: c.3709G>A
MANE Select: NM_001197104
dbSNP: rs572783697
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

Similar variants

KMT2A p.Val1237Leu 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
KMT2A p.Arg1081Ter 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-val1237met (accessed [today's date]).

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