Is KDM6B p.Trp1471Ter (c.4412G>A) pathogenic?

KDM6B p.Trp1471Ter (c.4412G>A) is classified Likely pathogenic in KDM6B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-16). Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities.

How common is KDM6B p.Trp1471Ter (c.4412G>A) in the general population?

KDM6B p.Trp1471Ter (c.4412G>A) is absent from gnomAD v4.1 (gnomAD).

KDM6B p.Trp1471Ter

Q: What condition is associated with KDM6B p.Trp1471Ter (c.4412G>A)?

KDM6B p.Trp1471Ter (c.4412G>A) is associated with neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (ClinVar).

c.4412G>A · rs2544534309 · VCV2442025

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 20 of 24
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	53.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: KDM6B
Protein: p.Trp1471Ter
Coding: c.4412G>A
MANE Select: NM_001348716
dbSNP: rs2544534309
Type: single nucleotide variant
Location: chr17:7852280 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.54 · 6 PDB
Residue 1471: the jmjc domain; a UniProt-annotated variant site (in nedsst); a β-strand

Full KDM6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM6B p.Arg1499Ter Pathogenic/Likely pathogenic ★★ same condition
KDM6B p.Arg166Ter Pathogenic ★★ same condition
KDM6B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same condition
KDM6B p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
KDM6B p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
KDM6B p.Ala750Thr Uncertain significance ★★ ⚠ same condition
KDM6B p.Ala808Ser Uncertain significance ★★ ⚠ same condition
KDM6B p.Arg1016Trp 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/kdm6b-p-trp1471ter (accessed [today's date]).

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