Is KDM4B p.Pro573Ser (c.1717C>T) pathogenic?

KDM4B p.Pro573Ser (c.1717C>T) is classified Uncertain significance in KDM4B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-04). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.0056%, sas); Associated with KDM4B-related disorder.

What condition is associated with KDM4B p.Pro573Ser (c.1717C>T)?

KDM4B p.Pro573Ser (c.1717C>T) is associated with KDM4B-related disorder (ClinVar).

How common is KDM4B p.Pro573Ser (c.1717C>T) in the general population?

KDM4B p.Pro573Ser (c.1717C>T) is very rare (popmax 0.0056%, sas) (gnomAD).

What do computational predictors say about KDM4B p.Pro573Ser (c.1717C>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

KDM4B p.Pro573Ser

c.1717C>T · rs747372978 · VCV2629868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0056%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KDM4B-related disorder

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.28	donor gain · deltas
Constraint at this position
Conservation	phyloP 1	GERP -0.11, phastCons 0.003
Regional constraint	o/e 1.06	unconstrained · MANE · 21 kb · p 0.26 · regional, not allelic
Overall
CADD	15.67	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 0.0056% South Asian · 5/89,318 alleles

Filtering AF 0.00214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00139%

Overall 0.000343% 5/1,456,304 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: KDM4B
Protein: p.Pro573Ser
Coding: c.1717C>T
MANE Select: NM_015015
dbSNP: rs747372978
Type: single nucleotide variant
Location: chr19:5131477 (GRCh38)
Gene constraint: LOEUF 0.371 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.50 · 6 PDB
Residue 573: the 'disordered' region

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

Disease context

KDM4B-related disorder

Similar variants

KDM4B p.Asp117Gly Uncertain significance ★★ ⚠ same condition
KDM4B p.Val1063Ala Uncertain significance ★★ ⚠ same condition
KDM4B p.Gln914Ter Likely pathogenic ★ same condition
KDM4B p.Ala759Val Uncertain significance ★ ⚠ same condition
KDM4B p.Arg111Trp Uncertain significance ★ ⚠ same condition
KDM4B p.Arg19Cys Uncertain significance ★ ⚠ same condition
KDM4B p.Gln542Glu Uncertain significance ⚠ same condition
KDM4B p.Glu979Asp 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/kdm4b-p-pro573ser (accessed [today's date]).

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