Is KDM5C p.Arg943Ter (c.2827C>T) pathogenic?

KDM5C p.Arg943Ter (c.2827C>T) is classified Pathogenic/Likely pathogenic in KDM5C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-01). Absent from gnomAD v4.1; Associated with KDM5C-related disorder.

What condition is associated with KDM5C p.Arg943Ter (c.2827C>T)?

KDM5C p.Arg943Ter (c.2827C>T) is associated with KDM5C-related disorder, syndromic X-linked intellectual disability Claes-Jensen type (ClinVar).

How common is KDM5C p.Arg943Ter (c.2827C>T) in the general population?

KDM5C p.Arg943Ter (c.2827C>T) is absent from gnomAD v4.1 (gnomAD).

KDM5C p.Arg943Ter

c.2827C>T · VCV3897952

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

KDM5C-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 19 of 26
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Overall
CADD	36.0	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: KDM5C
Protein: p.Arg943Ter
Coding: c.2827C>T
MANE Select: NM_004187
Type: single nucleotide variant
Location: chrX:53196840 (GRCh38)
Structure: AlphaFold pLDDT 72.50 · 2 PDB

Full KDM5C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KDM5C-related disorder

Also linked: syndromic X-linked intellectual disability Claes-Jensen type

Similar variants

KDM5C p.Arg943Gln Uncertain significance ★ ⚠ same residue
KDM5C p.Arg332Ter Pathogenic ★★ same condition
KDM5C p.Arg599Cys Pathogenic/Likely pathogenic ★★ same condition
KDM5C p.Arg681Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5C p.Arg750Trp Likely pathogenic ★★ same condition
KDM5C p.Arg828Ter Pathogenic ★★ same condition
KDM5C p.Arg929Ter Pathogenic/Likely pathogenic ★★ same condition
KDM5C p.Gln1020Ter Pathogenic ★★ 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/kdm5c-p-arg943ter (accessed [today's date]).

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