Is KDM4E p.Arg121Pro (c.362G>C) pathogenic?

KDM4E p.Arg121Pro (c.362G>C) is classified Uncertain significance in KDM4E (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely pathogenic (0.6269); Absent from gnomAD v4.1.

How common is KDM4E p.Arg121Pro (c.362G>C) in the general population?

KDM4E p.Arg121Pro (c.362G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM4E p.Arg121Pro (c.362G>C)?

AlphaMissense predicts likely pathogenic (score 0.6269) — an in-silico prediction, not a clinical call.

KDM4E p.Arg121Pro

c.362G>C · rs781997196 · VCV2495443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6269 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6269	likely pathogenic
REVEL	0.129	moderately benign-leaning
SaProt	LLR -10.12	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -2.1, phastCons 0.034
Regional constraint	o/e 0.73	unconstrained · MANE · 677 bp · p 4.7e-06 · regional, not allelic
Overall
CADD	16.95	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KDM4E
Protein: p.Arg121Pro
Coding: c.362G>C
MANE Select: NM_001161630
dbSNP: rs781997196
Type: single nucleotide variant
Location: chr11:95025919 (GRCh38)
Structure: AlphaFold pLDDT 76.85 · 1 PDB
Residue 121: an α-helix

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-arg121pro (accessed [today's date]).

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