Is KDM4B p.Phe268Ser (c.803T>C) pathogenic?

KDM4B p.Phe268Ser (c.803T>C) is classified Uncertain significance in KDM4B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1.

How common is KDM4B p.Phe268Ser (c.803T>C) in the general population?

KDM4B p.Phe268Ser (c.803T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM4B p.Phe268Ser (c.803T>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

KDM4B p.Phe268Ser

c.803T>C · rs2145871774 · VCV1327270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 2% in KDM4B
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -14.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 63 kb · p 3.1e-22 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: KDM4B
Protein: p.Phe268Ser
Coding: c.803T>C
MANE Select: NM_015015
dbSNP: rs2145871774
Type: single nucleotide variant
Location: chr19:5082389 (GRCh38)
Gene constraint: LOEUF 0.371 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.50 · 6 PDB
Residue 268: the jmjc domain; a β-strand

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-phe268ser (accessed [today's date]).

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