Is KDM4B p.Pro427Ser (c.1279C>T) pathogenic?

KDM4B p.Pro427Ser (c.1279C>T) is classified Uncertain significance in KDM4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely benign (0.0682); Ultra-rare (popmax 0.0611%, eas); Associated with Inborn genetic diseases.

What condition is associated with KDM4B p.Pro427Ser (c.1279C>T)?

KDM4B p.Pro427Ser (c.1279C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KDM4B p.Pro427Ser (c.1279C>T) in the general population?

KDM4B p.Pro427Ser (c.1279C>T) is ultra-rare (popmax 0.0611%, eas) (gnomAD).

What do computational predictors say about KDM4B p.Pro427Ser (c.1279C>T)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

KDM4B p.Pro427Ser

c.1279C>T · VCV4042282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0611%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.17	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 -0.17	GERP -0.12
Regional constraint	o/e 1.06	unconstrained · MANE · 21 kb · p 0.26 · regional, not allelic
Overall
CADD	0.367	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 0.0611% East Asian · 25/40,894 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0362%

Overall 0.00201% 28/1,391,692 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0611%	1,636
European (non-Finnish)	0.000262%	381,505

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.Pro427Ser
Coding: c.1279C>T
MANE Select: NM_015015
Type: single nucleotide variant
Location: chr19:5119816 (GRCh38)
Gene constraint: LOEUF 0.371 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.50 · 6 PDB
Residue 427: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM4B c.432+1G>A Pathogenic/Likely pathogenic ★★ same condition
KDM4B p.His768Arg Likely pathogenic ★★ same condition
KDM4B p.Ala187Thr Uncertain significance ★★ ⚠ same condition
KDM4B p.Ala759Thr Uncertain significance ★★ ⚠ same condition
KDM4B p.Arg1020His Uncertain significance ★★ ⚠ same condition
KDM4B p.Arg1035Cys Uncertain significance ★★ ⚠ same condition
KDM4B p.Arg57Trp Uncertain significance ★★ ⚠ same condition
KDM4B p.Arg828Cys 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-pro427ser (accessed [today's date]).

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