Is KDM4E p.Pro320Arg (c.959C>G) pathogenic?

KDM4E p.Pro320Arg (c.959C>G) is classified Uncertain significance in KDM4E (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.1804); Absent from gnomAD v4.1.

How common is KDM4E p.Pro320Arg (c.959C>G) in the general population?

KDM4E p.Pro320Arg (c.959C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM4E p.Pro320Arg (c.959C>G)?

AlphaMissense predicts likely benign (score 0.1804) — an in-silico prediction, not a clinical call.

KDM4E p.Pro320Arg

c.959C>G · rs2496510610 · VCV3113834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1804 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1804	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.1
Regional constraint	o/e 1.03	unconstrained · MANE · 839 bp · p 0.58 · regional, not allelic
Overall
CADD	14.15	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

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.Pro320Arg
Coding: c.959C>G
MANE Select: NM_001161630
dbSNP: rs2496510610
Type: single nucleotide variant
Location: chr11:95026516 (GRCh38)
Structure: AlphaFold pLDDT 76.85 · 1 PDB
Residue 320: 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-pro320arg (accessed [today's date]).

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