Is KDM4E p.Leu369Pro (c.1106T>C) pathogenic?

KDM4E p.Leu369Pro (c.1106T>C) is classified Uncertain significance in KDM4E (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely benign (0.0876); Very rare (popmax 8.72e-05%, nfe).

How common is KDM4E p.Leu369Pro (c.1106T>C) in the general population?

KDM4E p.Leu369Pro (c.1106T>C) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about KDM4E p.Leu369Pro (c.1106T>C)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

KDM4E p.Leu369Pro

c.1106T>C · VCV4543075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -13.42	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -2.8
Regional constraint	o/e 1.03	unconstrained · MANE · 839 bp · p 0.58 · regional, not allelic
Overall
CADD	10.96	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,912 alleles

Overall 7.22e-05% 1/1,384,940 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: KDM4E
Protein: p.Leu369Pro
Coding: c.1106T>C
MANE Select: NM_001161630
Type: single nucleotide variant
Location: chr11:95026663 (GRCh38)
Structure: AlphaFold pLDDT 76.85 · 1 PDB

Full KDM4E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KDM4E p.Ala187= Likely benign ★★ same type
KDM4E p.Cys381Tyr Benign ★★ same type
KDM4E p.Gln42Arg Benign ★★ same type
KDM4E p.Thr190= Likely benign ★★ same type
KDM4E p.Ala224Asp Uncertain significance ★ ⚠ same type
KDM4E p.Ala265Val Uncertain significance ★ ⚠ same type
KDM4E p.Ala287Thr Uncertain significance ★ ⚠ same type
KDM4E p.Ala406Thr Uncertain significance ★ ⚠ 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/kdm4e-p-leu369pro (accessed [today's date]).

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