Is KMT2E p.Pro264Ser (c.790C>T) pathogenic?

KMT2E p.Pro264Ser (c.790C>T) is classified Uncertain significance in KMT2E (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.2186); Very rare (popmax 0.000513%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KMT2E p.Pro264Ser (c.790C>T)?

KMT2E p.Pro264Ser (c.790C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KMT2E p.Pro264Ser (c.790C>T) in the general population?

KMT2E p.Pro264Ser (c.790C>T) is very rare (popmax 0.000513%, nfe) (gnomAD).

What do computational predictors say about KMT2E p.Pro264Ser (c.790C>T)?

AlphaMissense predicts likely benign (score 0.2186) — an in-silico prediction, not a clinical call.

KMT2E p.Pro264Ser

c.790C>T · rs146629053 · VCV3116071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2186 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000513%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2186	likely benign
REVEL	0.458	indeterminate
SaProt	LLR -4.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,718 bp · p 0.21 · regional, not allelic
Overall
CADD	26.3	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000513% European (non-Finnish) · 6/1,170,218 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000376% 6/1,597,840 alleles · very rare exomes 4/1,447,462 · genomes 2/150,378 · joint denominator

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: KMT2E
Protein: p.Pro264Ser
Coding: c.790C>T
MANE Select: NM_182931
dbSNP: rs146629053
Type: single nucleotide variant
Location: chr7:105076984 (GRCh38)
Gene constraint: LOEUF 0.217 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 44.57 · 3 PDB
Residue 264: the 'disordered' region; a UniProt-annotated variant site (in odluro)

Full KMT2E 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

KMT2E p.Arg874Ter Pathogenic/Likely pathogenic ★★ same condition
KMT2E c.768+5A>G Uncertain significance ★★ same condition
KMT2E p.Arg1100Gln Uncertain significance ★★ ⚠ same condition
KMT2E p.Arg656Gln Uncertain significance ★★ ⚠ same condition
KMT2E p.Arg669Ile Uncertain significance ★★ ⚠ same condition
KMT2E p.Asn1140Asp Uncertain significance ★★ ⚠ same condition
KMT2E p.Asn1233Lys Uncertain significance ★★ ⚠ same condition
KMT2E p.Asn772Ser Uncertain significance ★★ ⚠ 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/kmt2e-p-pro264ser (accessed [today's date]).

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