Is KDM4B p.Pro692Ser (c.2074C>T) pathogenic?

KDM4B p.Pro692Ser (c.2074C>T) is classified Uncertain significance in KDM4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-29). AlphaMissense: ambiguous (0.5211); Absent from gnomAD v4.1.

How common is KDM4B p.Pro692Ser (c.2074C>T) in the general population?

KDM4B p.Pro692Ser (c.2074C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM4B p.Pro692Ser (c.2074C>T)?

AlphaMissense predicts ambiguous (score 0.5211) — an in-silico prediction, not a clinical call.

KDM4B p.Pro692Ser

c.2074C>T · VCV4088068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5211 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5211	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -5.27	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP -2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,451 bp · p 0.41 · regional, not allelic
Overall
CADD	25.6	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: KDM4B
Protein: p.Pro692Ser
Coding: c.2074C>T
MANE Select: NM_015015
Type: single nucleotide variant
Location: chr19:5134050 (GRCh38)
Gene constraint: LOEUF 0.371 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.50 · 6 PDB

Full KDM4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KDM4B c.432+1G>A Pathogenic/Likely pathogenic ★★ same type
KDM4B p.His768Arg Likely pathogenic ★★ same type
KDM4B p.Ala187Thr Uncertain significance ★★ ⚠ same type
KDM4B p.Ala651Asp Uncertain significance ★★ ⚠ same type
KDM4B p.Ala706Gly Uncertain significance ★★ ⚠ same type
KDM4B p.Ala759Thr Uncertain significance ★★ ⚠ same type
KDM4B p.Arg1020His Uncertain significance ★★ ⚠ same type
KDM4B p.Arg1035Cys 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/kdm4b-p-pro692ser (accessed [today's date]).

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