Is KMT2B p.Arg287Cys (c.859C>T) pathogenic?

KMT2B p.Arg287Cys (c.859C>T) is classified Benign in KMT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: ambiguous (0.4048); Ultra-rare (popmax 0.0179%, eas).

How common is KMT2B p.Arg287Cys (c.859C>T) in the general population?

KMT2B p.Arg287Cys (c.859C>T) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about KMT2B p.Arg287Cys (c.859C>T)?

AlphaMissense predicts ambiguous (score 0.4048) — an in-silico prediction, not a clinical call.

KMT2B p.Arg287Cys

c.859C>T · rs150247325 · VCV2954998

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4048 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Computational evidence

Protein change
AlphaMissense	0.4048	ambiguous
REVEL	0.423	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 3.4	GERP -0.17, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 4,448 bp · p 0.014 · regional, not allelic
Overall
CADD	19.06	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 0.0179% East Asian · 8/44,682 alleles

Filtering AF 0.00887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00643%

Overall 0.00274% 44/1,608,306 alleles · ultra-rare exomes 36/1,456,076 · genomes 8/152,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,585
African / African-American	0.00667%	14,983
Remaining individualsnot grpmax-eligible	0.00482%	20,765
European (non-Finnish)	0.00238%	42,056

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: KMT2B
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_014727
dbSNP: rs150247325
Type: single nucleotide variant
Location: chr19:35720206 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 287: the 'disordered' region; a UniProt-annotated variant site (in dyt28)

Full KMT2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KMT2B p.Arg287His Likely benign ★ same residue
KMT2B p.Ala1616Val Likely pathogenic ★★ same type
KMT2B p.Ala2641Thr Likely pathogenic ★★ same type
KMT2B p.Arg142Ter Pathogenic ★★ same type
KMT2B p.Arg1597Trp Pathogenic/Likely pathogenic ★★ same type
KMT2B p.Arg1705Ter Pathogenic ★★ same type
KMT2B p.Arg2565Gly Likely pathogenic ★★ same type
KMT2B p.Arg2610Cys Likely 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/kmt2b-p-arg287cys (accessed [today's date]).

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